Epidemiological and genomic characteristics of global blaNDM-carrying Escherichia coli

Epidemiological and genomic characteristics of global blaNDM-carrying Escherichia coli | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Epidemiological and genomic characteristics of global blaNDM-carrying Escherichia coli Changyu Xia, Ruyu Yan, Chang Liu, Junbin Zhai, Jie Zeng, Wei Chen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3955970/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jun, 2024 Read the published version in Annals of Clinical Microbiology and Antimicrobials → Version 1 posted 10 You are reading this latest preprint version Abstract Background Escherichia. coli is the most frequent host for New Delhi metallo-β-lactamase (NDM) which hydrolyzes almost all β-lactams except aztreonam. The worldwide spread of bla NDM-carrying E. coli heavily threatens public health. Objective This study aimed to explore the global genomic epidemiology of bla NDM- carrying E. coli isolates, providing information for preventing the dissemination of such strains. Methods Global E. coli genomes were downloaded from NCBI database and bla NDM was detected using BLASTP. Per software was used to extract meta information on hosts, resources, collection data, and countries of origin from GenBank. The sequence types (STs) and distribution of antimicrobial resistance gene (ARG) were analyzed by CLC Workbench; Plasmid replicons, serotypes and virulence genes (VFs) were analyzed by submitting the genomes to the websites. Statistical analyses were performed to access the relationships among ARGs and plasmid replicons. Results Until March 2023, 1,774 out of 33,055 isolates collected during 2003–2022 were found to contain bla NDM in total. Among them, 15 bla NDM variants were found with bla NDM-5 (74.1%) being most frequent, followed by bla NDM-1 (16.6%) and bla NDM-9 (4.6%). Among the 213 ARGs identified, 27 bla CTX-M and 39 bla TEM variants were found with bla CTX-M-15 (n = 438, 24.7%) and bla TEM-1B (n = 1092, 61.6%) being the most frequent ones, respectively. In addition, 546 (30.8%) plasmids mediated ampC genes, 508 (28.6%) exogenously acquired 16S rRNA methyltransferase encoding genes and 262 (14.8%) mcr were also detected. Among the 232 distinct STs, ST167 (17.2%) were the most prevalent. As for plasmids, more than half of isolates contained IncFII, IncFIB and IncX3. The VF terC , gad , traT and iss as well as the serotypes O101:H9 (n = 231, 13.0%), O8:H9 (n = 115, 6.5%) and O9:H30 (n = 99, 5.6%) were frequently observed. Conclusions The study delves into the intricate relationship between plasmid types, virulence factors, and ARGs, which provides valuable insights for clinical treatment and public health interventions, and serves as a critical resource for guiding future research, surveillance, and implementation of effective strategies to address the challenges posed by bla NDM-carrying E. coli . The findings underscore the urgent need for sustained global collaboration, surveillance efforts, and antimicrobial stewardship to mitigate the impact of these highly resistant strains on public health. Carbapenem-resistant Escherichia coli blaNDM Serotype Virulence factors Sequence types Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Escherichia coli , a rod-shaped, gram-negative bacterium, predominantly resides in the lower intestinal tract of warm-blooded animals, including humans. Known as one of the most frequent opportunistic pathogens, it is a leading cause of urinary, bloodstream, and wound infections in both community and hospital settings. Within the realm of antibiotic resistance, a significant concern is the emergence of New Delhi metallo-β-lactamase (NDM), a member of the β1 metallo-β-lactamase class, capable of hydrolyzing almost all β-lactams except monobactams. It’s initially identified in a Swedish patient in New Delhi, India, in 2008 [ 1 ]. At present, the bla NDM variants have now spread across more than 60 species in 11 bacterial families, with E. coli being the predominant carrier of the bla NDM gene [ 2 ]. Strains belonging to the ST167, ST410, and ST617 lineages are the most prevalent clones [ 3 , 4 ]. Geographically, the Indian subcontinent, the Middle East, and the Balkans are the most epidemic regions [ 5 ]. The global dissemination of bla NDM-carrying strains poses a considerable challenge for clinical management and public health, due to the heightened mortality rates associated with infections caused by these strains. Besides, various antimicrobial resistance genes (ARGs), such as non-NDM carbapenem hydrolyzing β-lactamases (CHβLs), extended-spectrum β-lactamases (ESBLs), plasmid-mediated quinolone resistance genes (PMQRs), and exogenously acquired 16S rRNA methyltransferase (16S-RMTase) genes, are often co-harbored with bla NDM in E. coli , leading to multi-drug resistance or pan-drug resistance [ 6 , 7 ], thereby limiting antimicrobial treatment options for E. coli infection in clinical settings. The escalating prevalence of bla NDM worldwide can be attributed to global travel and extensive antibiotic use, recognized as key population risk factors linked to the dispersal of bla NDM. Notably, the spread of bla NDM genes is primarily facilitated by mobile genetic elements (MGEs), with plasmids being the most common carriers. These bla NDM-carrying plasmids typically fall under limited replicon types, such as IncX3, IncFII, or IncC [ 8 ]. Despite numerous studies on the epidemiological characteristics of Carbapenem-resistant E. coli (CREC), comprehensive data on the virulence factors (VFs), serotypes, and sequence types (STs) of bla NDM-carrying E. coli remain limited. This study aims to characterize the global epidemiological features of bla NDM-carrying E. coli by leveraging genomic data from GenBank. The investigation includes an analysis of the distribution of other ARGs, plasmid replicons, VFs, serotypes, and STs to provide a thorough genomic characterization. Additionally, the study explores the consistency in the distribution of plasmid replicons and VFs, as well as VFs and ARGs, shedding light on potential associations between these key elements. Material and methods 1. Download of E. coli genome data Sequence files of all 33055 E. coli genomes (updated to 2023.03.09) were downloaded in batch from NCBI ( https://www.ncbi.nlm.nih.gov/genome/browse/#!/overview/ ) using the aspera high-speed download tool. For all annotated genomes, the protein coding gene sequence of each genome is obtained in batch from GenBank file by using self-made Perl script. All genomes were qualified with completeness > 90%, contamination < 5%, and contig quantity ≤ 500 and N50 ≥ 40,000. 2. bla NDM identification All bla NDM sequences were obtained from the NCBI Biological Resistance Reference Gene Database ( https://www.ncbi.nlm.nih.gov/pathogens/refgene/#gene_family:(blaNDM) . BLASTP was performed, with thresholds being set as expected value = 1e-5, coverage ≥ 60%, identity ≥ 90%, and match length = subject gene length. Finally, the results were processed by Perl program to obtain the detailed distribution of bla NDM gene in E. coli genomes. 3. Extraction of meta-information on the bla NDM-carrying E. coli Meta information on hosts, resources, collection data, and countries of origin was extracted from GenBank using Per software. This information was integrated with the ARGs, STs, VFs and serotypes into the same excel for further analysis. 4. Investigation into the prevalence of antimicrobial resistance genes The distribution of other ARGs was investigated using CLC workbench version 21.0.1. The fasta file was input into the files in CLC Workbench using standard import, and after the consensus sequence was extracted, the prevalence of ARGs was analyzed using the ResFinder database for comparison. The results were exported as scv files, and further sorted for analysis. 5. Sequence types STs of bla NDM-carrying E. coli were identified using CLC workbench 21.0.1. After consensus sequences were extracted, STs were analyzed using multi-locus sequence typing (MLST) with E. coli (Oxford) as the reference database. 6. Distributions of plasmid replicons, VFs, and serotypes Genomes were submitted to the Center for Genomic Epidemiology ( http://www.Genomicepidemiology.org/ ). Plasmid Finder 2.1 was used to identify plasmid replicons, and VFs were analyzed by Virulence Finder 2.0. Moreover, serotypes were identified by Serotype Finder 2.0. 7. Statistical analyses Correlation analyses were performed using SPSS 22.0. The distribution consistency of VFs and ARGs was tested by McNimar analysis, and a p-value of > 0.05 was taken as the consistency between them. Results The prevalent characteristics of bla NDM-carrying E. coli Totally, 33,055 E. coli isolates were downloaded from NCBI database and the time span was from 2003 to 2022. Of which, 1,774 were identified to be positive for the bla NDM gene (Additional file 1). These isolates were obtained from 43 countries across 6 continents (Fig. 1 ), which were as follows: Asia (n = 1376, 77.6%), Europe (n = 196, 11.0%), North America (n = 63, 3.6%), Africa (n = 29, 1.6%), South America (n = 29, 1.6%), and Oceania (n = 2, 0.1%). Of concern, China (n = 1127, 63.5%), India (n = 115, 6.5%), and France (n = 83, 4.7%) were the primary contributors, submitting the highest number of genomes, following closely were the USA (n = 56), Germany (n = 33), Thailand (n = 30), United Kingdom (n = 21), Bangladesh (n = 20), South Korea (n = 19), Lebanon (n = 16), and Pakistan (n = 11). The origin of the remaining 79 isolates was unspecified. Of 1,774 bla NDM genes, 15 distinct bla NDM variants were identified. While the number of bla NDM-carrying E. coli showed a gradual increase each year, it surged significantly in 2015 (n = 350). This elevated level was sustained from 2016 to 2019, followed by a decline from 2020 to 2022 (Fig. 2 ). Regarding the sources of the bla NDM-carrying E. coli isolates (Table 1 ), it was observed that Homo sapiens accounted for the majority, constituting 59.6% (n = 1,057) of the total. These isolates were predominantly sourced from urine (n = 232), blood (n = 162), rectal/anal swabs (n = 149), sputum (n = 81), and fecal samples (n = 86). Animals comprised 27.4% (n = 486) of the isolates, with chickens (n = 182), pigs (n = 59), and flies (n = 46) being the most prevalent species. The primary sources for animal isolates included fecal samples, cloaca swabs, and various organs (intestine/liver/other). Notably, bla NDM-carrying strains were also detected in the environment, accounting for 13.0% (n = 231) of the isolates. These environmental sources included water, hospitals, and various food items. Table 1 The hosts and sample types of global bla NDM-carrying E. coli isolates Hosts (n) Sample types (n) Homo sapiens (1057) Urine (232), blood (162), rectal/anal swab (149), fecal sample (86), sputum (81), bile (13), catheter tip (5), ear swab (1), vaginal swab (1), wound/other body fluids/pus (133), NA (194) Animals (486) Chicken (182) Fecal sample (63), cloaca swab (83), intestine/liver/other organs (30), NA (8) Pig (59) Fecal sample (50), NA (9) Fly (46) Fecal sample (46) Swine (42) Fecal sample (38), NA (4) poultry (37) Fecal sample (33), Droppings (2), NA (2) Waterfowl (27) NA (27) Others (93) Fecal sample (35), Ear swab (2), liver (2), NA (54) Environments (231) Water (28), hospital (20), Milk (2), environment (13), leaf rape (1), medical sewage (1), NA (166) NA, not applicable. Wide distribution of various resistance genes among bla NDM-carrying E. coli Among the 1,774 bla NDM-carrying isolates, 15 distinct variants were identified, with bla NDM-5 being the most prevalent (n = 1,315, 74.1%), followed by bla NDM-1 (n = 295, 16.6%) and bla NDM-9 (n = 82, 4.6%). Other variants included bla NDM-7, bla NDM-4, bla NDM-6, bla NDM-13, bla NDM-3, bla NDM-15, bla NDM-19, bla NDM-16, bla NDM-20, bla NDM-21, bla NDM-22, and bla NDM-24, each with lower frequencies. Geographically, bla NDM-5 dominated in Asia, Europe, Africa, and North America, constituting 62.0%-77.0% of cases (Fig. 1 ). Notably, South America exhibited a distinct pattern, with bla NDM-1 being the most common variant, representing 93.0% of cases. A comprehensive analysis of ARGs in bla NDM-carrying strains revealed 213 different types. Among them, CHßLs encoding genes including 8 bla KPC-2, 1 bla IMP-1, 34 bla OXA-181, 10 bla OXA-232, 5 bla OXA-244 and 5 bla OXA-48 were identified. Moreover, 27 bla CTX-M and 39 bla TEM variants were detected with bla CTX-M-15 (n = 438, 24.7%), bla CTX-M-55 (n = 300, 16.9%), bla CTX-M-14 (n = 204, 11.5%), bla CTX-M-65 (n = 147, 8.3%) and bla TEM-1B (n = 1092, 61.6%) being the most frequent ones, respectively. In addition, 546 (30.8%) plasmids mediated ampC genes, including 501 bla CMY and 45 bla DHA as well as 508 (28.6%) 16S-RMTase encoding genes, including 409 rmtB , 55 rmtC and 44 armA were found. Of significant concern, 262 (14.8%) co-existing mcr genes were also detected, with mcr 1.1 being the most prevalent genotype (n = 249, 14.0%). Furthermore, 467 (26.3%) fosfomycin resistance genes including 459 fosA3 and 8 fosA4 as well as 546 (30.8%) aac(6’)-ib-cr conferring resistance to amikacin and fluoroquinolones in addition to 805 (45.4%) PMQRs including 239 oqxAB , 126 qepA , and 440 qnr were identified. Other main ARGs detected were shown in Fig. 3 . Multiple distinct Sequence types were identified with several high-risk clones being prevalent A total of 232 distinct STs were identified among the bla NDM-carrying E. coli isolates. The most prevalent was ST167 (n = 306, 17.2%), followed by ST410 (n = 174, 9.8%), ST361 (n = 108, 6.1%), ST405 (n = 85, 4.8%), ST156 (n = 74, 4.2%), ST10 (n = 73, 4.1%), ST48 (n = 59, 3.3%), ST617 (n = 53, 3.0%), ST101 (n = 50, 2.8%), ST648 (n = 44, 2.5%), and ST746 (n = 38, 2.1%). Several other STs were also identified, with each less than 30. Geographically, the distribution of STs varied. ST167 was predominant in both Asia and North America, ST361 was endemic in Europe, and ST410 emerged as the predominant clone in Africa, with ST10 dominating in South America (Fig. 1 ). Virulence factors A total of 170 distinct VFs were identified among the bla NDM-carrying E. coli isolates. The most prevalent VF was terC (n = 1,766, 99.5%). Notably, more than half of the isolates carried four specific VFs: gad (83.4%, n = 1,480), traT (67.9%, n = 1,205), and iss (51.3%, n = 910). Several other VFs were also frequently detected, including sitA (n = 756, 42.6%), hra (n = 689, 38.8%), lpfA (n = 631, 35.6%), fyuA (n = 561, 31.6%), and irp2 (n = 560, 31.6%). Of significant concern is the differential distribution of the predominantly prevalent VFs among the endemic clones. Notably, lpfA was primarily distributed among ST410 and ST156, while iss was predominantly concentrated in ST167 and ST156. The dominance of fyuA and irp2 was observed among ST405, with ST361 and ST405 being the most frequent carriers for sitA . Multiple Plasmid replicons were found among bla NDM -carrying E. coli which may facilitate the spread of antimicrobial resistance genes Various plasmid replicons were identified, with IncFII (n = 1,163, 65.6%) emerging as the most prevalent. Following closely were IncFIB (n = 1,157, 65.2%), IncX3 (n = 888, 50.1%), IncFIA (n = 756, 42.6%), COL (n = 440, 24.8%), IncY (n = 338, 19.1%), IncI1-I (n = 321, 18.1%), P0111 (n = 306, 17.2%), IncHI2 (n = 287, 16.2%), IncQ1 (n = 194, 10.9%), IncI (n = 190, 10.7%), IncFIC (n = 179, 10.1%), IncC (n = 174, 9.8%), IncR (n = 114, 6.4%), IncX1 (n = 128, 7.2%), IncN (n = 77, 4.3%), and several other rare plasmid replicons. Analysis revealed that 44.7–66.8% of bla NDM-5-carrying strains carried IncFII, IncFIB, IncX3, and IncFIA plasmids (Table 2 ). For bla NDM-1-carrying strains, over half carried IncFII and IncFIB plasmids, with IncFIA and Col being relatively highly prevalent. IncFIB, IncFII, and Col were frequently carried by bla NDM-9 positive strains. Notably, IncFIA was particularly prevalent, reaching 80.9%, in bla NDM-7-carrying strains, followed by IncFIB, IncFII, and IncX3. Table 2 Plasmids distribution among different bla NDM-carrying strains. IncFII (n = 1163) IncFIB (n = 1157) IncX3 (n = 888) IncFIA (n = 756) Col (n = 440) IncY (n = 338) IncI1-I (n = 321) P0111 (n = 306) IncHI2 (n = 287) bla NDM-5 (n = 1315) 878 (66.8%) 860 (65.4%) 752 (57.2%) 588 (44.7%) 312 (18.2%) 254 (19.3%) 251 (19.1%) 232 (17.6%) 211 (16.0%) bla NDM-1 (n = 295) 191 (64.7%) 176 (59.7%) 67 (22.7%) 111 (37.6%) 102 (34.6%) 43 (14.6%) 53 (18.0%) 55 (18.6%) 49 (16.6%) bla NDM-9 (n = 82) 47 (57.3%) 62 (75.6%) 2 (2.4%) 12 (14.6%) 38 (46.3%) 19 (23.2%) 23 (28.0%) 20 (24.4%) 16 (19.5%) bla NDM-7 (n = 32) 21 (65.6%) 23 (71.9%) 21 (65.6%) 17 (80.9%) 6 (18.8%) 6 (18.8%) 2 (6.2%) 3 (9.4%) 3 (9.4%) Analyzing the consistency between prevalent plasmids and resistant/virulent genes (Table 3 ) revealed correlations between the prevalence of mph(A) and tra(T) and the plasmid replicons IncFII and IncFIB (p > 0.05). The incidences of aph(6)-Id , aadA2 , aph(3'')-Ib , dfrA12 , and iss were all correlated with the presence of plasmid IncX3. Additionally, the distribution of bla OXA-1, iucC , and capU was consistent with the presence of plasmid Col. Table 3 Consistency analysis between plasmids and resistant/virulent genes Genes IncFII (n = 1163) IncFIB (n = 1157) IncX3 (n = 888) IncFIA (n = 756) Col (n = 440) IncY (n = 338) IncI1-I (n = 321) P0111 (n = 306) IncHI2 (n = 287) sul1 (n = 1234) 0.006 0.000 0.000 0.000 0.000 0.000 0.010 0.000 0.000 mph(A) (n = 1173) 0.747* 0.588* 0.000 0.000 0.000 0.000 0.000 0.000 0.000 bla TEM-1b (n = 1092) 0.000 0.000 0.000 0.003 0.000 0.000 0.000 0.000 0.000 tet(A) (n = 1084) 0.008 0.012 0.000 0.000 0.000 0.000 0.000 0.000 0.000 aph(6)-Id (n = 913) 0.000 0.000 0.428* 0.000 0.000 0.000 0.000 0.000 0.000 aadA2 (n = 906) 0.000 0.000 0.586* 0.000 0.000 0.000 0.000 0.000 0.000 aph(3'')-Ib (n = 898) 0.000 0.000 0.767* 0.000 0.000 0.000 0.000 0.000 0.000 dfrA12 (n = 826) 0.000 0.000 0.053* 0.016 0.000 0.000 0.000 0.000 0.000 floR (n = 826) 0.000 0.000 0.032 0.028 0.000 0.000 0.000 0.000 0.000 bla OXA-1 (n = 459) 0.000 0.000 0.000 0.000 0.475* 0.000 0.000 0.000 0.000 terC (n = 1766) 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 Gad (n = 1480) 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 traT (n = 1205) 0.093* 0.086* 0.000 0.000 0.000 0.000 0.000 0.000 0.000 iss (n = 910) 0.000 0.000 0.464* 0.000 0.000 0.000 0.000 0.000 0.000 sitA (n = 756) 0.000 0.000 0.000 1.000 0.000 0.000 0.000 0.000 0.000 hra (n = 689) 0.000 0.000 0.000 0.020 0.000 0.000 0.000 0.000 0.000 lpfA (n = 631) 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 fyuA (n = 561) 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 irp2 (n = 560) 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 ompT (n = 530) 0.000 0.000 0.000 0.000 0.001 0.000 0.000 0.000 0.000 iucC (n = 456) 0.000 0.000 0.000 0.000 0.565* 0.000 0.000 0.000 0.000 capU (n = 485) 0.000 0.000 0.000 0.000 0.105* 0.000 0.000 0.000 0.000 *p > 0.05 was considered as the consistency between resistant/virulent genes and plasmid replicons. The prevalence of ARGs and VFs among epidemic clones ST167, ST410, ST361, ST405 and ST156 were demonstrated in the Fig. 4 . More than 42.5% of them carried bla TEM, bla CTX-M, bla NDM-5, traT , gad and terC , constituting a basic resistant and virulent profile. In detail, ST167 clones exhibited high incidences of iss and hra ; S156 showed a high carriage of mcr , rmt , lpdA iss and hra . Notably, ST410 clones demonstrated nearly 100% carriage of lpfA and high incidences of aac(6’)-ib-cr and bla OXA, while ST405 showed a high prevalence of fyuA , irp2 , sitA , traT , gad and rmt . This highlights the distinct prevalence patterns of ARGs among different STs, emphasizing the diversity in resistance and virulence profiles associated with specific E. coli lineages. A large number of serotypes detected among bla NDM -carrying E. coli with O101:H9 and O8:H9 being the predominate A total of 91 distinct O types were identified, with O101 (n = 391, 22.0%), O8 (n = 179, 10.1%), O9 (n = 154, 8.7%), and O102 (n = 92, 5.2%) emerging as the dominant ones. Among the 43 H types, H9 (n = 470, 26.5%) was the most prevalent, followed by H30 (n = 140, 7.9%), H6 (n = 130, 7.3%), H10 (n = 121, 6.8%), and H5 (n = 114, 6.4%). Over 100 distinct serotypes were identified, with O101:H9 (n = 231, 13.0%), O8:H9 (n = 115, 6.5%), O9:H30 (n = 99, 5.6%), O102:H6 (n = 86, 4.8%), and O101:H10 (n = 77, 4.3%) being the most frequent. Discussion The increasing prevalence of bla NDM-carrying E. coli presents significant challenges to clinical treatment and global public health, prompting a critical need to bolster infection control measures in hospitals. The epidemiological and genomic characterization of 1,774 bla NDM-carrying E. coli isolates from 43 countries (2003–2022) provides valuable insights for guiding clinical treatment strategies and implementing preventative measures. Our study showed that prevalence rates of bla NDM-carrying E. coli varied globally, with Asia reporting the highest, followed by Europe (11.0%), America (5.2%), Africa (1.6%), and Oceania (0.01%). These rates closely align with a meta-analysis of 110 studies from 2008–2018 [ 9 ], confirming the high prevalence of such strain in Asia. In addition, we identified a notable surge of bla NDM in E. coli isolates during 2015–2019, with bla NDM-5 emerging as the most frequent variant. Consistent with this, an upward trend in bla NDM-carrying Enterobacterale has been observed in France since 2012, in Switzerland since 2013, and in Germany from 2013 to 2019 [ 10 – 13 ]. Particularly concerning is the rapid global spread of bla NDM-5 producing E. coli , contributing to an epidemic situation in India, China, and sub-Saharan Africa [ 5 , 14 ]. Furthermore, the global prevalence of bla NDM experienced a decline in 2020 and 2021, likely attributed to some sequence data not being released at the time of our data retrieval in 2023. Moreover, our study showed that animals and environments constituted 40% of the studied resources, which may relate with the use of carbapenem antibiotics in poultry breeding. Notably, as observed in other studies, there was a substantial prevalence of bla NDM-5 in poultry and farm environments, which may be spread from healthcare settings [ 15 ]. Of great note, our findings align with previous research, affirming that all bla NDM-positive E. coli isolates in our study co-carried additional ARGs. The most prevalent among these were sul1 and sul2 , encoding an alternative dihydropteroate synthase, emphasizing the need for cautious prescription of sulfonamides targeting CREC. Furthermore, we observed the coexistence of bla ESBL, particularly bla TEM-1b and bla CTX-M-15, with the bla NDM-5 gene, consistent with prior reports [ 12 , 16 ]. This underscores the complexity of resistance profiles and emphasizes the importance of comprehensive antimicrobial stewardship. It is noteworthy that in our study, 61.1% of bla NDM-carrying E. coli concurrently carried the tet(A) gene, known to result in reduced susceptibility to tigecycline, signaling a need for cautious use of tigecycline in treating such strains [ 17 , 18 ]. Additionally, a significant 14.0% of bla NDM-carrying E. coli harbored the mcr 1.1 gene, a horizontally transmitted colistin resistance gene [ 19 ]. This finding is of great concern as it poses a challenge to the effectiveness of colistin in treating infections caused by these strains. Further complicating matters, our study identified nine derivatives of mcr ( mcr-2 to mcr-10 ) [ 20 ], suggesting a potential reduction in polymyxin sensitivity among bla NDM-positive strains due to the widespread presence of mcr . Furthermore, 46.6% of bla NDM-positive strains simultaneously carried the Trimethoprim-resistance gene dfrA12 and Florfenicol resistance genes floR , indicating a multi-drug resistance profile. Notably, in strains carrying both mcr-1 and bla NDM-5, our study revealed IncFIB as the main plasmid carrying both genes, deviating from previous observations [ 21 , 22 ], possibly due to the extensive inclusion of strains in our analysis. This emphasizes the intricate interplay of resistance mechanisms and highlights the necessity for vigilant antimicrobial management strategies. ST analysis revealed a diverse array of STs among bla NDM-carrying E. coli . Notably, ST167 dominated in China and India, while ST361 was predominant in Europe, diverging from previous reports which indicated that ST101 and ST131 are the most prevalent clones in Asia, ST101 and ST405 are the dominant STs in Europe [ 9 ]. This discrepancy may arise from the focus on bla NDM-carrying E. coli in our study, reflecting distinct strain compositions. Consistent with other studies, ST167 and ST410 emerged as international epidemic clones linked with bla NDM-5 [ 23 , 24 ]. Contrary to these findings, no specific ST linkage was observed for bla NDM-1[ 5 ], although some strains were assigned to ST410, ST156, ST167, ST10, and ST101. Remarkably, ST13, recognized as the pandemic clone associated with global dissemination of the bla CTX-M-15 [ 25 , 26 ], was identified in only 17 bla NDM-carrying E. coli isolates, underscoring a divergence in the dissemination patterns of different ARGs. Among various VFs, over half of the strains carried terC , gad , traT , and iss . terC , encoding a tellurium iron resistance protein [ 27 ]. The gad gene, facilitating survival in acidic environments, and the traT gene, which encodes protections, along with iss , sitA , and hra genes being associated with urinary tract infection, were also prevalent [ 28 , 29 ]. Importantly, the distribution of predominant VFs varied significantly among the prevailing clones, highlighting the intricate relationship between genetic backgrounds and virulence traits [ 30 ]. IncFII and IncFIB emerged as the predominant plasmids in all bla NDM-carrying isolates, showcasing a correlation with the mph(A) and tra(T) genes. Following closely were IncX3 and IncFIA. Notably, it’s reported that IncX3-type plasmids are recognized as key contributors to horizontal transmission of bla NDM in CREC [ 31 ] and IncFIB is prevalent especially in bla NDM-1-carrying E. coli in Greece [ 32 ]. Serotype O101, associated with both animal and human diseases, is commonly detected among pathogenic E. coli [ 33 ]. In our study, O101:H9 emerged as the most prevalent, even though reports of this specific serotype are limited. Interestingly, O101:H9 has been linked to possible international dissemination via migratory birds [ 34 ], emphasizing the importance of employing techniques such as multiplex PCR or whole-genome sequencing that go beyond focusing solely on serotype O157:H7 in clinical laboratories. These diverse molecular findings underscore the necessity for ongoing surveillance of bla NDM-carrying E. coli strains. To our best knowledge, this study represents the largest comprehensive report on the prevalence and genetic characterization of bla NDM-carrying E. coli worldwide, utilizing whole-genome data. However, it is crucial to acknowledge certain limitations. Firstly, the inclusion criteria were limited to data available on the NCBI database, potentially introducing selection bias. Secondly, the study's ability to fully capture the global prevalence of bla NDM-carrying E. coli is constrained by the insufficient availability of genome data from many countries. Thirdly, the absence of detailed epidemiological data limits the exploration of factors such as prior exposure to healthcare settings and environmental influences, which may play a significant role in the global transmission of bla NDM-carrying E. coli . Despite these limitations, this study offers valuable insights into the epidemiology and genomic characteristics of bla NDM-carrying E. coli on a global scale. Conclusions This study offers a comprehensive understanding of the prevalence, genetic diversity, and associated factors of bla NDM-carrying E. coli , submitted by 43 countries over the period 2003–2022. bla NDM-5 is the predominant variant, identified in diverse ST and O:H serotypes, highlighting the complexity and adaptability of these multidrug-resistant strains. The study delves into the intricate relationship between plasmid types, virulence factors, and ARGs, providing valuable insights for clinical treatment and public health interventions. As the global threat of antimicrobial resistance continues to escalate, this study serves as a critical resource for guiding future research, surveillance, and implementation of effective strategies to address the challenges posed by bla NDM-carrying E. coli . The findings underscore the urgent need for sustained global collaboration, surveillance efforts, and antimicrobial stewardship to mitigate the impact of these highly resistant strains on public health. Declarations Ethics approval and consent to participate Not applicable (All the data were downloaded from NCBI database). Consent for publication Acknowledgements We would like to express our gratitude to everyone who participated in this research study. Consent for publication Not applicable. Data availability statement The original contributions presented in this study are included in this article/Supplementary material, further inquiries can be directed to the corresponding authors. Author Affiliations : Department of Laboratory Medicine, Peking University First Hospital, Beijing, China Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Jiangsu, China Clinical Research Center, the Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, China Author contributions XC contributed to the experimental design of the study. CX, RY, JZ, JZ and XC performed data acquisition and statistical analysis. CX, RY and XC performed bioinformatics analysis and writing. All authors contributed to the article and approved the submitted version. Corresponding author Correspondence to Xiaoli Cao. Funding This study was supported by the National Natural Science Foundation of China (81902124). Conflict of interest statement The authors declare no conflict of interest. References Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, et al. 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Protein Eng Des Sel. 2017;30(3):235–44. 10.1093/protein/gzw076 . Ovi F, Zhang L, Nabors H, Jia L, Adhikari P. A compilation of virulence-associated genes that are frequently reported in avian pathogenic Escherichia coli (APEC) compared to other E. coli. J Appl Microbiol. 2023;134(3). 10.1093/jambio/lxad014 . Xu J, Guo H, Li L, He F. Molecular epidemiology and genomic insights into the transmission of carbapenem-resistant NDM-producing Escherichia coli. Comput Struct Biotechnol J. 2023;21:847–55. 10.1016/j.csbj.2023.01.004 . Tsilipounidaki K, Florou Z, Skoulakis A, Fthenakis GC, Miriagou V, Petinaki E. Diversity of Bacterial Clones and Plasmids of NDM-1 Producing Escherichia coli Clinical Isolates in Central Greece. Microorganisms. 2023;11(2). 10.3390/microorganisms11020516 . Chirila F, Tabaran A, Fit N, Nadas G, Mihaiu M, Tabaran F, et al. Concerning Increase in Antimicrobial Resistance in Shiga Toxin-Producing Escherichia coli Isolated from Young Animals during 1980–2016. Microbes Environ. 2017;32(3):252–9. 10.1264/jsme2.ME17023 . He WY, Zhang XX, Gao GL, Gao MY, Zhong FG, Lv LC, et al. Clonal spread of Escherichia coli O101: H9-ST10 and O101: H9-ST167 strains carrying fosA3 and bla (CTX-M-14) among diarrheal calves in a Chinese farm, with Australian Chroicocephalus as the possible origin of E. coli O101: H9-ST10. Zool Res. 2021;42(4):461–8. 10.24272/j.issn.2095-8137.2021.153 . Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.xlsx Cite Share Download PDF Status: Published Journal Publication published 20 Jun, 2024 Read the published version in Annals of Clinical Microbiology and Antimicrobials → Version 1 posted Editorial decision: Accepted 15 Jun, 2024 Reviews received at journal 10 Jun, 2024 Reviewers agreed at journal 10 Jun, 2024 Reviews received at journal 03 Jun, 2024 Reviewers agreed at journal 25 May, 2024 Reviewers agreed at journal 05 Mar, 2024 Reviewers invited by journal 04 Mar, 2024 Editor assigned by journal 03 Mar, 2024 Submission checks completed at journal 15 Feb, 2024 First submitted to journal 14 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3955970","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272970689,"identity":"acffd048-1734-4c42-8db3-cec123904a2d","order_by":0,"name":"Changyu Xia","email":"","orcid":"","institution":"Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Changyu","middleName":"","lastName":"Xia","suffix":""},{"id":272970690,"identity":"9e2e2428-b7fa-43c1-9701-34a4d54a7909","order_by":1,"name":"Ruyu Yan","email":"","orcid":"","institution":"Nanjing Drum Tower Hospital Clinical College of Nanjing University 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coli\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e worldwide. \u003c/strong\u003eHollow and solid pie charts of each continent represent\u003cem\u003e bla\u003c/em\u003eNDM\u003cem\u003e \u003c/em\u003eand STs, respectively.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3955970/v1/9352cf46c1e17f4dd7b56a20.png"},{"id":51226034,"identity":"8b3dd0df-9c8e-4b58-b529-64d94bed9951","added_by":"auto","created_at":"2024-02-16 11:45:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":22892,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNumber of global \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003ebla\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003eNDM-carrying \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eEscherichia coli\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e isolates submitted per year.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3955970/v1/7cc955f1424f34b95f8b145c.png"},{"id":51226032,"identity":"b7be9876-c7a9-4b20-a7bd-3bf20d321223","added_by":"auto","created_at":"2024-02-16 11:45:36","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":177678,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe antimicrobial resistance genes identified among 1774 \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003ebla\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003eNDM-carrying \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eEscherichia coli\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e.\u003c/strong\u003e3A. all the antimicrobial resistance genes; 3B. \u003cem\u003emcr\u003c/em\u003e variants; 3C, \u003cem\u003ebla\u003c/em\u003eOXA variants; 3D. \u003cem\u003ebla\u003c/em\u003eCMY variants; 3E. \u003cem\u003ebla\u003c/em\u003eNDM variants; 3F. \u003cem\u003ebla\u003c/em\u003eCTX-M variants; 3G. \u003cem\u003ebla\u003c/em\u003eTEM variants.\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3955970/v1/9ec4cba0fac2901e983bca98.png"},{"id":51226035,"identity":"b169b02f-df7d-4467-a7ae-771805c6153e","added_by":"auto","created_at":"2024-02-16 11:45:37","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":17462,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe prevalence of prevalent antimicrobial resistance genes and virulent factors among epidemic clones.\u003c/strong\u003e Antimicrobial resistance genes were \u003cem\u003eaac(6’)-ib-cr\u003c/em\u003e, \u003cem\u003emcr\u003c/em\u003e, \u003cem\u003ermt\u003c/em\u003e, \u003cem\u003eqnr\u003c/em\u003e, \u003cem\u003ebla\u003c/em\u003eOXA, \u003cem\u003ebla\u003c/em\u003eTEM, \u003cem\u003ebla\u003c/em\u003eCTX-M, \u003cem\u003ebla\u003c/em\u003eNDM-5; Virulence factors were \u003cem\u003eterC\u003c/em\u003e,\u003cem\u003e gad\u003c/em\u003e, \u003cem\u003etraT\u003c/em\u003e, \u003cem\u003eiss\u003c/em\u003e, \u003cem\u003esitA\u003c/em\u003e,\u003cem\u003e hra\u003c/em\u003e, \u003cem\u003elpfA\u003c/em\u003e, \u003cem\u003efyuA\u003c/em\u003e, \u003cem\u003eirp2\u003c/em\u003e.\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-3955970/v1/e8fd1e021626a95ee3409071.png"},{"id":58841960,"identity":"9e610443-c13b-4f9b-8663-33bb244cf03f","added_by":"auto","created_at":"2024-06-22 00:29:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1486240,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3955970/v1/7b6a7b1c-38bf-4a50-b38e-1aa157f4d051.pdf"},{"id":51226540,"identity":"4e6cb9ca-645f-46b8-988f-66604175f50b","added_by":"auto","created_at":"2024-02-16 11:53:36","extension":"xlsx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":207222,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3955970/v1/d0c6e93a99cb32acab4fb8ec.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Epidemiological and genomic characteristics of global blaNDM-carrying Escherichia coli","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eEscherichia coli\u003c/em\u003e, a rod-shaped, gram-negative bacterium, predominantly resides in the lower intestinal tract of warm-blooded animals, including humans. Known as one of the most frequent opportunistic pathogens, it is a leading cause of urinary, bloodstream, and wound infections in both community and hospital settings. Within the realm of antibiotic resistance, a significant concern is the emergence of New Delhi metallo-β-lactamase (NDM), a member of the β1 metallo-β-lactamase class, capable of hydrolyzing almost all β-lactams except monobactams. It\u0026rsquo;s initially identified in a Swedish patient in New Delhi, India, in 2008 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. At present, the \u003cem\u003ebla\u003c/em\u003eNDM variants have now spread across more than 60 species in 11 bacterial families, with \u003cem\u003eE. coli\u003c/em\u003e being the predominant carrier of the \u003cem\u003ebla\u003c/em\u003eNDM gene [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Strains belonging to the ST167, ST410, and ST617 lineages are the most prevalent clones [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Geographically, the Indian subcontinent, the Middle East, and the Balkans are the most epidemic regions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The global dissemination of \u003cem\u003ebla\u003c/em\u003eNDM-carrying strains poses a considerable challenge for clinical management and public health, due to the heightened mortality rates associated with infections caused by these strains. Besides, various antimicrobial resistance genes (ARGs), such as non-NDM carbapenem hydrolyzing β-lactamases (CHβLs), extended-spectrum β-lactamases (ESBLs), plasmid-mediated quinolone resistance genes (PMQRs), and exogenously acquired 16S rRNA methyltransferase (16S-RMTase) genes, are often co-harbored with \u003cem\u003ebla\u003c/em\u003eNDM in \u003cem\u003eE. coli\u003c/em\u003e, leading to multi-drug resistance or pan-drug resistance [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], thereby limiting antimicrobial treatment options for \u003cem\u003eE. coli\u003c/em\u003e infection in clinical settings.\u003c/p\u003e \u003cp\u003eThe escalating prevalence of \u003cem\u003ebla\u003c/em\u003eNDM worldwide can be attributed to global travel and extensive antibiotic use, recognized as key population risk factors linked to the dispersal of \u003cem\u003ebla\u003c/em\u003eNDM. Notably, the spread of \u003cem\u003ebla\u003c/em\u003eNDM genes is primarily facilitated by mobile genetic elements (MGEs), with plasmids being the most common carriers. These \u003cem\u003ebla\u003c/em\u003eNDM-carrying plasmids typically fall under limited replicon types, such as IncX3, IncFII, or IncC [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Despite numerous studies on the epidemiological characteristics of Carbapenem-resistant \u003cem\u003eE. coli\u003c/em\u003e (CREC), comprehensive data on the virulence factors (VFs), serotypes, and sequence types (STs) of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e remain limited.\u003c/p\u003e \u003cp\u003eThis study aims to characterize the global epidemiological features of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e by leveraging genomic data from GenBank. The investigation includes an analysis of the distribution of other ARGs, plasmid replicons, VFs, serotypes, and STs to provide a thorough genomic characterization. Additionally, the study explores the consistency in the distribution of plasmid replicons and VFs, as well as VFs and ARGs, shedding light on potential associations between these key elements.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003e\u003cstrong\u003e1. Download of\u003c/strong\u003e \u003cstrong\u003eE. coli\u003c/strong\u003e \u003cstrong\u003egenome data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSequence files of all 33055 \u003cem\u003eE. coli\u003c/em\u003e genomes (updated to 2023.03.09) were downloaded in batch from NCBI (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/genome/browse/#!/overview/\u003c/span\u003e\u003c/span\u003e) using the aspera high-speed download tool. For all annotated genomes, the protein coding gene sequence of each genome is obtained in batch from GenBank file by using self-made Perl script. All genomes were qualified with completeness\u0026thinsp;\u0026gt;\u0026thinsp;90%, contamination\u0026thinsp;\u0026lt;\u0026thinsp;5%, and contig quantity\u0026thinsp;\u0026le;\u0026thinsp;500 and N50\u0026thinsp;\u0026ge;\u0026thinsp;40,000.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. bla\u003c/strong\u003e \u003cstrong\u003eNDM identification\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll \u003cem\u003ebla\u003c/em\u003eNDM sequences were obtained from the NCBI Biological Resistance Reference Gene Database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/pathogens/refgene/#gene_family:(blaNDM)\u003c/span\u003e\u003c/span\u003e. BLASTP was performed, with thresholds being set as expected value\u0026thinsp;=\u0026thinsp;1e-5, coverage\u0026thinsp;\u0026ge;\u0026thinsp;60%, identity\u0026thinsp;\u0026ge;\u0026thinsp;90%, and match length\u0026thinsp;=\u0026thinsp;subject gene length. Finally, the results were processed by Perl program to obtain the detailed distribution of \u003cem\u003ebla\u003c/em\u003eNDM gene in \u003cem\u003eE. coli\u003c/em\u003e genomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3. Extraction of meta-information on the\u003c/strong\u003e \u003cstrong\u003ebla\u003c/strong\u003e\u003cstrong\u003eNDM-carrying\u003c/strong\u003e \u003cstrong\u003eE. coli\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMeta information on hosts, resources, collection data, and countries of origin was extracted from GenBank using Per software. This information was integrated with the ARGs, STs, VFs and serotypes into the same excel for further analysis.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003e4. Investigation into the prevalence of antimicrobial resistance genes\u003c/h2\u003e\n\u003cp\u003eThe distribution of other ARGs was investigated using CLC workbench version 21.0.1. The fasta file was input into the files in CLC Workbench using standard import, and after the consensus sequence was extracted, the prevalence of ARGs was analyzed using the ResFinder database for comparison. The results were exported as scv files, and further sorted for analysis.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003e5. Sequence types\u003c/h2\u003e\n\u003cp\u003eSTs of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e were identified using CLC workbench 21.0.1. After consensus sequences were extracted, STs were analyzed using multi-locus sequence typing (MLST) with \u003cem\u003eE. coli\u003c/em\u003e (Oxford) as the reference database.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003e6. Distributions of plasmid replicons, VFs, and serotypes\u003c/h2\u003e\n\u003cp\u003eGenomes were submitted to the Center for Genomic Epidemiology (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.Genomicepidemiology.org/\u003c/span\u003e\u003c/span\u003e). Plasmid Finder 2.1 was used to identify plasmid replicons, and VFs were analyzed by Virulence Finder 2.0. Moreover, serotypes were identified by Serotype Finder 2.0.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003e7. Statistical analyses\u003c/h2\u003e\n\u003cp\u003eCorrelation analyses were performed using SPSS 22.0. The distribution consistency of VFs and ARGs was tested by McNimar analysis, and a p-value of \u0026gt;\u0026thinsp;0.05 was taken as the consistency between them.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eThe prevalent characteristics of\u003c/b\u003e \u003cb\u003ebla\u003c/b\u003e\u003cb\u003eNDM-carrying\u003c/b\u003e \u003cb\u003eE. coli\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTotally, 33,055 \u003cem\u003eE. coli\u003c/em\u003e isolates were downloaded from NCBI database and the time span was from 2003 to 2022. Of which, 1,774 were identified to be positive for the \u003cem\u003ebla\u003c/em\u003eNDM gene (Additional file 1). These isolates were obtained from 43 countries across 6 continents (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), which were as follows: Asia (n\u0026thinsp;=\u0026thinsp;1376, 77.6%), Europe (n\u0026thinsp;=\u0026thinsp;196, 11.0%), North America (n\u0026thinsp;=\u0026thinsp;63, 3.6%), Africa (n\u0026thinsp;=\u0026thinsp;29, 1.6%), South America (n\u0026thinsp;=\u0026thinsp;29, 1.6%), and Oceania (n\u0026thinsp;=\u0026thinsp;2, 0.1%). Of concern, China (n\u0026thinsp;=\u0026thinsp;1127, 63.5%), India (n\u0026thinsp;=\u0026thinsp;115, 6.5%), and France (n\u0026thinsp;=\u0026thinsp;83, 4.7%) were the primary contributors, submitting the highest number of genomes, following closely were the USA (n\u0026thinsp;=\u0026thinsp;56), Germany (n\u0026thinsp;=\u0026thinsp;33), Thailand (n\u0026thinsp;=\u0026thinsp;30), United Kingdom (n\u0026thinsp;=\u0026thinsp;21), Bangladesh (n\u0026thinsp;=\u0026thinsp;20), South Korea (n\u0026thinsp;=\u0026thinsp;19), Lebanon (n\u0026thinsp;=\u0026thinsp;16), and Pakistan (n\u0026thinsp;=\u0026thinsp;11). The origin of the remaining 79 isolates was unspecified.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOf 1,774 \u003cem\u003ebla\u003c/em\u003eNDM genes, 15 distinct \u003cem\u003ebla\u003c/em\u003eNDM variants were identified. While the number of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e showed a gradual increase each year, it surged significantly in 2015 (n\u0026thinsp;=\u0026thinsp;350). This elevated level was sustained from 2016 to 2019, followed by a decline from 2020 to 2022 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRegarding the sources of the \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e isolates (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), it was observed that Homo sapiens accounted for the majority, constituting 59.6% (n\u0026thinsp;=\u0026thinsp;1,057) of the total. These isolates were predominantly sourced from urine (n\u0026thinsp;=\u0026thinsp;232), blood (n\u0026thinsp;=\u0026thinsp;162), rectal/anal swabs (n\u0026thinsp;=\u0026thinsp;149), sputum (n\u0026thinsp;=\u0026thinsp;81), and fecal samples (n\u0026thinsp;=\u0026thinsp;86). Animals comprised 27.4% (n\u0026thinsp;=\u0026thinsp;486) of the isolates, with chickens (n\u0026thinsp;=\u0026thinsp;182), pigs (n\u0026thinsp;=\u0026thinsp;59), and flies (n\u0026thinsp;=\u0026thinsp;46) being the most prevalent species. The primary sources for animal isolates included fecal samples, cloaca swabs, and various organs (intestine/liver/other). Notably, \u003cem\u003ebla\u003c/em\u003eNDM-carrying strains were also detected in the environment, accounting for 13.0% (n\u0026thinsp;=\u0026thinsp;231) of the isolates. These environmental sources included water, hospitals, and various food items.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe hosts and sample types of global \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e isolates\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHosts (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSample types (n)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHomo sapiens (1057)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUrine (232), blood (162), rectal/anal swab (149), fecal sample (86), sputum (81), bile (13), catheter tip (5), ear swab (1), vaginal swab (1), wound/other body fluids/pus (133), NA (194)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnimals (486)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChicken (182)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFecal sample (63), cloaca swab (83), intestine/liver/other organs (30), NA (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePig (59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFecal sample (50), NA (9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFly (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFecal sample (46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSwine (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFecal sample (38), NA (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epoultry (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFecal sample (33), Droppings (2), NA (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWaterfowl (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA (27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOthers (93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFecal sample (35), Ear swab (2), liver (2), NA (54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEnvironments (231)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWater (28), hospital (20), Milk (2), environment (13), leaf rape (1), medical sewage (1), NA (166)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNA, not applicable.\u003c/p\u003e \u003cp\u003e \u003cb\u003eWide distribution of various resistance genes among\u003c/b\u003e \u003cb\u003ebla\u003c/b\u003e\u003cb\u003eNDM-carrying\u003c/b\u003e \u003cb\u003eE. coli\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAmong the 1,774 \u003cem\u003ebla\u003c/em\u003eNDM-carrying isolates, 15 distinct variants were identified, with \u003cem\u003ebla\u003c/em\u003eNDM-5 being the most prevalent (n\u0026thinsp;=\u0026thinsp;1,315, 74.1%), followed by \u003cem\u003ebla\u003c/em\u003eNDM-1 (n\u0026thinsp;=\u0026thinsp;295, 16.6%) and \u003cem\u003ebla\u003c/em\u003eNDM-9 (n\u0026thinsp;=\u0026thinsp;82, 4.6%). Other variants included \u003cem\u003ebla\u003c/em\u003eNDM-7, \u003cem\u003ebla\u003c/em\u003eNDM-4, \u003cem\u003ebla\u003c/em\u003eNDM-6, \u003cem\u003ebla\u003c/em\u003eNDM-13, \u003cem\u003ebla\u003c/em\u003eNDM-3, \u003cem\u003ebla\u003c/em\u003eNDM-15, \u003cem\u003ebla\u003c/em\u003eNDM-19, \u003cem\u003ebla\u003c/em\u003eNDM-16, \u003cem\u003ebla\u003c/em\u003eNDM-20, \u003cem\u003ebla\u003c/em\u003eNDM-21, \u003cem\u003ebla\u003c/em\u003eNDM-22, and \u003cem\u003ebla\u003c/em\u003eNDM-24, each with lower frequencies. Geographically, \u003cem\u003ebla\u003c/em\u003eNDM-5 dominated in Asia, Europe, Africa, and North America, constituting 62.0%-77.0% of cases (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Notably, South America exhibited a distinct pattern, with \u003cem\u003ebla\u003c/em\u003eNDM-1 being the most common variant, representing 93.0% of cases.\u003c/p\u003e \u003cp\u003eA comprehensive analysis of ARGs in \u003cem\u003ebla\u003c/em\u003eNDM-carrying strains revealed 213 different types. Among them, CH\u0026szlig;Ls encoding genes including 8 \u003cem\u003ebla\u003c/em\u003eKPC-2, 1 \u003cem\u003ebla\u003c/em\u003eIMP-1, 34 \u003cem\u003ebla\u003c/em\u003eOXA-181, 10 \u003cem\u003ebla\u003c/em\u003eOXA-232, 5 \u003cem\u003ebla\u003c/em\u003eOXA-244 and 5 \u003cem\u003ebla\u003c/em\u003eOXA-48 were identified. Moreover, 27 \u003cem\u003ebla\u003c/em\u003eCTX-M and 39 \u003cem\u003ebla\u003c/em\u003eTEM variants were detected with \u003cem\u003ebla\u003c/em\u003eCTX-M-15 (n\u0026thinsp;=\u0026thinsp;438, 24.7%), \u003cem\u003ebla\u003c/em\u003eCTX-M-55 (n\u0026thinsp;=\u0026thinsp;300, 16.9%), \u003cem\u003ebla\u003c/em\u003eCTX-M-14 (n\u0026thinsp;=\u0026thinsp;204, 11.5%), \u003cem\u003ebla\u003c/em\u003eCTX-M-65 (n\u0026thinsp;=\u0026thinsp;147, 8.3%) and \u003cem\u003ebla\u003c/em\u003eTEM-1B (n\u0026thinsp;=\u0026thinsp;1092, 61.6%) being the most frequent ones, respectively. In addition, 546 (30.8%) plasmids mediated \u003cem\u003eampC\u003c/em\u003e genes, including 501 \u003cem\u003ebla\u003c/em\u003eCMY and 45 \u003cem\u003ebla\u003c/em\u003eDHA as well as 508 (28.6%) 16S-RMTase encoding genes, including 409 \u003cem\u003ermtB\u003c/em\u003e, 55 \u003cem\u003ermtC\u003c/em\u003e and 44 \u003cem\u003earmA\u003c/em\u003e were found. Of significant concern, 262 (14.8%) co-existing \u003cem\u003emcr\u003c/em\u003e genes were also detected, with \u003cem\u003emcr\u003c/em\u003e1.1 being the most prevalent genotype (n\u0026thinsp;=\u0026thinsp;249, 14.0%). Furthermore, 467 (26.3%) fosfomycin resistance genes including 459 \u003cem\u003efosA3\u003c/em\u003e and 8 \u003cem\u003efosA4\u003c/em\u003e as well as 546 (30.8%) \u003cem\u003eaac(6\u0026rsquo;)-ib-cr\u003c/em\u003e conferring resistance to amikacin and fluoroquinolones in addition to 805 (45.4%) PMQRs including 239 \u003cem\u003eoqxAB\u003c/em\u003e, 126 \u003cem\u003eqepA\u003c/em\u003e, and 440 \u003cem\u003eqnr\u003c/em\u003e were identified. Other main ARGs detected were shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMultiple distinct Sequence types were identified with several high-risk clones being prevalent\u003c/h2\u003e \u003cp\u003eA total of 232 distinct STs were identified among the \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e isolates. The most prevalent was ST167 (n\u0026thinsp;=\u0026thinsp;306, 17.2%), followed by ST410 (n\u0026thinsp;=\u0026thinsp;174, 9.8%), ST361 (n\u0026thinsp;=\u0026thinsp;108, 6.1%), ST405 (n\u0026thinsp;=\u0026thinsp;85, 4.8%), ST156 (n\u0026thinsp;=\u0026thinsp;74, 4.2%), ST10 (n\u0026thinsp;=\u0026thinsp;73, 4.1%), ST48 (n\u0026thinsp;=\u0026thinsp;59, 3.3%), ST617 (n\u0026thinsp;=\u0026thinsp;53, 3.0%), ST101 (n\u0026thinsp;=\u0026thinsp;50, 2.8%), ST648 (n\u0026thinsp;=\u0026thinsp;44, 2.5%), and ST746 (n\u0026thinsp;=\u0026thinsp;38, 2.1%). Several other STs were also identified, with each less than 30. Geographically, the distribution of STs varied. ST167 was predominant in both Asia and North America, ST361 was endemic in Europe, and ST410 emerged as the predominant clone in Africa, with ST10 dominating in South America (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eVirulence factors\u003c/h3\u003e\n\u003cp\u003eA total of 170 distinct VFs were identified among the \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e isolates. The most prevalent VF was \u003cem\u003eterC\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1,766, 99.5%). Notably, more than half of the isolates carried four specific VFs: \u003cem\u003egad\u003c/em\u003e (83.4%, n\u0026thinsp;=\u0026thinsp;1,480), \u003cem\u003etraT\u003c/em\u003e (67.9%, n\u0026thinsp;=\u0026thinsp;1,205), and \u003cem\u003eiss\u003c/em\u003e (51.3%, n\u0026thinsp;=\u0026thinsp;910). Several other VFs were also frequently detected, including \u003cem\u003esitA\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;756, 42.6%), \u003cem\u003ehra\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;689, 38.8%), \u003cem\u003elpfA\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;631, 35.6%), \u003cem\u003efyuA\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;561, 31.6%), and \u003cem\u003eirp2\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;560, 31.6%).\u003c/p\u003e \u003cp\u003eOf significant concern is the differential distribution of the predominantly prevalent VFs among the endemic clones. Notably, \u003cem\u003elpfA\u003c/em\u003e was primarily distributed among ST410 and ST156, while \u003cem\u003eiss\u003c/em\u003e was predominantly concentrated in ST167 and ST156. The dominance of \u003cem\u003efyuA\u003c/em\u003e and \u003cem\u003eirp2\u003c/em\u003e was observed among ST405, with ST361 and ST405 being the most frequent carriers for \u003cem\u003esitA\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMultiple Plasmid replicons were found among\u003c/b\u003e \u003cb\u003ebla\u003c/b\u003eNDM\u003cb\u003e-carrying\u003c/b\u003e \u003cb\u003eE. coli\u003c/b\u003e \u003cb\u003ewhich may facilitate the spread of antimicrobial resistance genes\u003c/b\u003e\u003c/p\u003e \u003cp\u003eVarious plasmid replicons were identified, with IncFII (n\u0026thinsp;=\u0026thinsp;1,163, 65.6%) emerging as the most prevalent. Following closely were IncFIB (n\u0026thinsp;=\u0026thinsp;1,157, 65.2%), IncX3 (n\u0026thinsp;=\u0026thinsp;888, 50.1%), IncFIA (n\u0026thinsp;=\u0026thinsp;756, 42.6%), COL (n\u0026thinsp;=\u0026thinsp;440, 24.8%), IncY (n\u0026thinsp;=\u0026thinsp;338, 19.1%), IncI1-I (n\u0026thinsp;=\u0026thinsp;321, 18.1%), P0111 (n\u0026thinsp;=\u0026thinsp;306, 17.2%), IncHI2 (n\u0026thinsp;=\u0026thinsp;287, 16.2%), IncQ1 (n\u0026thinsp;=\u0026thinsp;194, 10.9%), IncI (n\u0026thinsp;=\u0026thinsp;190, 10.7%), IncFIC (n\u0026thinsp;=\u0026thinsp;179, 10.1%), IncC (n\u0026thinsp;=\u0026thinsp;174, 9.8%), IncR (n\u0026thinsp;=\u0026thinsp;114, 6.4%), IncX1 (n\u0026thinsp;=\u0026thinsp;128, 7.2%), IncN (n\u0026thinsp;=\u0026thinsp;77, 4.3%), and several other rare plasmid replicons.\u003c/p\u003e \u003cp\u003eAnalysis revealed that 44.7\u0026ndash;66.8% of \u003cem\u003ebla\u003c/em\u003eNDM-5-carrying strains carried IncFII, IncFIB, IncX3, and IncFIA plasmids (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). For \u003cem\u003ebla\u003c/em\u003eNDM-1-carrying strains, over half carried IncFII and IncFIB plasmids, with IncFIA and Col being relatively highly prevalent. IncFIB, IncFII, and Col were frequently carried by \u003cem\u003ebla\u003c/em\u003eNDM-9 positive strains. Notably, IncFIA was particularly prevalent, reaching 80.9%, in \u003cem\u003ebla\u003c/em\u003eNDM-7-carrying strains, followed by IncFIB, IncFII, and IncX3.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePlasmids distribution among different \u003cem\u003ebla\u003c/em\u003eNDM-carrying strains.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncFII\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1163)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIncFIB\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1157)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncX3\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;888)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncFIA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;756)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCol\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;440)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIncY\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;338)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIncI1-I\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;321)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP0111\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;306)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIncHI2\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;287)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ebla\u003c/b\u003e\u003cb\u003eNDM-5\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1315)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e878\u003c/p\u003e \u003cp\u003e(66.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e860\u003c/p\u003e \u003cp\u003e(65.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e752\u003c/p\u003e \u003cp\u003e(57.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e588\u003c/p\u003e \u003cp\u003e(44.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e312\u003c/p\u003e \u003cp\u003e(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e254\u003c/p\u003e \u003cp\u003e(19.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e251\u003c/p\u003e \u003cp\u003e(19.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e232\u003c/p\u003e \u003cp\u003e(17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e211\u003c/p\u003e \u003cp\u003e(16.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ebla\u003c/b\u003e\u003cb\u003eNDM-1\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;295)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e191\u003c/p\u003e \u003cp\u003e(64.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e176\u003c/p\u003e \u003cp\u003e(59.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67\u003c/p\u003e \u003cp\u003e(22.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e111\u003c/p\u003e \u003cp\u003e(37.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e102\u003c/p\u003e \u003cp\u003e(34.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e43\u003c/p\u003e \u003cp\u003e(14.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e53\u003c/p\u003e \u003cp\u003e(18.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e55\u003c/p\u003e \u003cp\u003e(18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e49\u003c/p\u003e \u003cp\u003e(16.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ebla\u003c/b\u003e\u003cb\u003eNDM-9\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003cp\u003e(57.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003cp\u003e(75.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003cp\u003e(14.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e38\u003c/p\u003e \u003cp\u003e(46.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19\u003c/p\u003e \u003cp\u003e(23.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23\u003c/p\u003e \u003cp\u003e(28.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e(24.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e16\u003c/p\u003e \u003cp\u003e(19.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ebla\u003c/b\u003e\u003cb\u003eNDM-7\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e(65.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003cp\u003e(71.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e(65.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003cp\u003e(80.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(18.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(18.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(9.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAnalyzing the consistency between prevalent plasmids and resistant/virulent genes (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) revealed correlations between the prevalence of \u003cem\u003emph(A)\u003c/em\u003e and \u003cem\u003etra(T)\u003c/em\u003e and the plasmid replicons IncFII and IncFIB (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The incidences of \u003cem\u003eaph(6)-Id\u003c/em\u003e, \u003cem\u003eaadA2\u003c/em\u003e, \u003cem\u003eaph(3'')-Ib\u003c/em\u003e, \u003cem\u003edfrA12\u003c/em\u003e, and \u003cem\u003eiss\u003c/em\u003e were all correlated with the presence of plasmid IncX3. Additionally, the distribution of \u003cem\u003ebla\u003c/em\u003eOXA-1, \u003cem\u003eiucC\u003c/em\u003e, and \u003cem\u003ecapU\u003c/em\u003e was consistent with the presence of plasmid Col.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eConsistency analysis between plasmids and resistant/virulent genes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGenes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncFII\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1163)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIncFIB\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1157)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncX3\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;888)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncFIA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;756)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCol\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;440)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIncY\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;338)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIncI1-I\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;321)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP0111\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;306)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIncHI2\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;287)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003esul1\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1234)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003emph(A)\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1173)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.747*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.588*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ebla\u003c/em\u003eTEM-1b (n\u0026thinsp;=\u0026thinsp;1092)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003etet(A)\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1084)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eaph(6)-Id\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;913)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.428*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eaadA2\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;906)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.586*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eaph(3'')-Ib\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;898)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.767*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003edfrA12\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;826)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.053*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003efloR\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;826)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ebla\u003c/em\u003eOXA-1 (n\u0026thinsp;=\u0026thinsp;459)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.475*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eterC\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1766)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGad\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1480)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003etraT\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1205)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.093*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.086*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eiss\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;910)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.464*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003esitA\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;756)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ehra\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;689)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003elpfA\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;631)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003efyuA\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;561)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eirp2\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;560)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eompT\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;530)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eiucC\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;456)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.565*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ecapU\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;485)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.105*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*p\u0026thinsp;\u0026gt;\u0026thinsp;0.05 was considered as the consistency between resistant/virulent genes and plasmid replicons.\u003c/p\u003e \u003cp\u003eThe prevalence of ARGs and VFs among epidemic clones ST167, ST410, ST361, ST405 and ST156 were demonstrated in the Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. More than 42.5% of them carried \u003cem\u003ebla\u003c/em\u003eTEM, \u003cem\u003ebla\u003c/em\u003eCTX-M, \u003cem\u003ebla\u003c/em\u003eNDM-5, \u003cem\u003etraT\u003c/em\u003e, \u003cem\u003egad\u003c/em\u003e and \u003cem\u003eterC\u003c/em\u003e, constituting a basic resistant and virulent profile. In detail, ST167 clones exhibited high incidences of \u003cem\u003eiss\u003c/em\u003e and \u003cem\u003ehra\u003c/em\u003e; S156 showed a high carriage of \u003cem\u003emcr\u003c/em\u003e, \u003cem\u003ermt\u003c/em\u003e, \u003cem\u003elpdA iss\u003c/em\u003e and \u003cem\u003ehra\u003c/em\u003e. Notably, ST410 clones demonstrated nearly 100% carriage of \u003cem\u003elpfA\u003c/em\u003e and high incidences of \u003cem\u003eaac(6\u0026rsquo;)-ib-cr\u003c/em\u003e and \u003cem\u003ebla\u003c/em\u003eOXA, while ST405 showed a high prevalence of \u003cem\u003efyuA\u003c/em\u003e, \u003cem\u003eirp2\u003c/em\u003e, \u003cem\u003esitA\u003c/em\u003e, \u003cem\u003etraT\u003c/em\u003e, \u003cem\u003egad\u003c/em\u003e and \u003cem\u003ermt\u003c/em\u003e. This highlights the distinct prevalence patterns of ARGs among different STs, emphasizing the diversity in resistance and virulence profiles associated with specific \u003cem\u003eE. coli\u003c/em\u003e lineages.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eA large number of serotypes detected among\u003c/b\u003e \u003cb\u003ebla\u003c/b\u003eNDM\u003cb\u003e-carrying\u003c/b\u003e \u003cb\u003eE. coli\u003c/b\u003e \u003cb\u003ewith O101:H9 and O8:H9 being the predominate\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA total of 91 distinct O types were identified, with O101 (n\u0026thinsp;=\u0026thinsp;391, 22.0%), O8 (n\u0026thinsp;=\u0026thinsp;179, 10.1%), O9 (n\u0026thinsp;=\u0026thinsp;154, 8.7%), and O102 (n\u0026thinsp;=\u0026thinsp;92, 5.2%) emerging as the dominant ones. Among the 43 H types, H9 (n\u0026thinsp;=\u0026thinsp;470, 26.5%) was the most prevalent, followed by H30 (n\u0026thinsp;=\u0026thinsp;140, 7.9%), H6 (n\u0026thinsp;=\u0026thinsp;130, 7.3%), H10 (n\u0026thinsp;=\u0026thinsp;121, 6.8%), and H5 (n\u0026thinsp;=\u0026thinsp;114, 6.4%). Over 100 distinct serotypes were identified, with O101:H9 (n\u0026thinsp;=\u0026thinsp;231, 13.0%), O8:H9 (n\u0026thinsp;=\u0026thinsp;115, 6.5%), O9:H30 (n\u0026thinsp;=\u0026thinsp;99, 5.6%), O102:H6 (n\u0026thinsp;=\u0026thinsp;86, 4.8%), and O101:H10 (n\u0026thinsp;=\u0026thinsp;77, 4.3%) being the most frequent.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe increasing prevalence of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e presents significant challenges to clinical treatment and global public health, prompting a critical need to bolster infection control measures in hospitals. The epidemiological and genomic characterization of 1,774 \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e isolates from 43 countries (2003\u0026ndash;2022) provides valuable insights for guiding clinical treatment strategies and implementing preventative measures.\u003c/p\u003e \u003cp\u003eOur study showed that prevalence rates of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e varied globally, with Asia reporting the highest, followed by Europe (11.0%), America (5.2%), Africa (1.6%), and Oceania (0.01%). These rates closely align with a meta-analysis of 110 studies from 2008\u0026ndash;2018 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], confirming the high prevalence of such strain in Asia. In addition, we identified a notable surge of \u003cem\u003ebla\u003c/em\u003eNDM in \u003cem\u003eE. coli\u003c/em\u003e isolates during 2015\u0026ndash;2019, with \u003cem\u003ebla\u003c/em\u003eNDM-5 emerging as the most frequent variant. Consistent with this, an upward trend in \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eEnterobacterale\u003c/em\u003e has been observed in France since 2012, in Switzerland since 2013, and in Germany from 2013 to 2019 [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Particularly concerning is the rapid global spread of \u003cem\u003ebla\u003c/em\u003eNDM-5 producing \u003cem\u003eE. coli\u003c/em\u003e, contributing to an epidemic situation in India, China, and sub-Saharan Africa [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, the global prevalence of \u003cem\u003ebla\u003c/em\u003eNDM experienced a decline in 2020 and 2021, likely attributed to some sequence data not being released at the time of our data retrieval in 2023. Moreover, our study showed that animals and environments constituted 40% of the studied resources, which may relate with the use of carbapenem antibiotics in poultry breeding. Notably, as observed in other studies, there was a substantial prevalence of \u003cem\u003ebla\u003c/em\u003eNDM-5 in poultry and farm environments, which may be spread from healthcare settings [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOf great note, our findings align with previous research, affirming that all \u003cem\u003ebla\u003c/em\u003eNDM-positive \u003cem\u003eE. coli\u003c/em\u003e isolates in our study co-carried additional ARGs. The most prevalent among these were \u003cem\u003esul1\u003c/em\u003e and \u003cem\u003esul2\u003c/em\u003e, encoding an alternative dihydropteroate synthase, emphasizing the need for cautious prescription of sulfonamides targeting CREC. Furthermore, we observed the coexistence of \u003cem\u003ebla\u003c/em\u003eESBL, particularly \u003cem\u003ebla\u003c/em\u003eTEM-1b and \u003cem\u003ebla\u003c/em\u003eCTX-M-15, with the \u003cem\u003ebla\u003c/em\u003eNDM-5 gene, consistent with prior reports [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This underscores the complexity of resistance profiles and emphasizes the importance of comprehensive antimicrobial stewardship. It is noteworthy that in our study, 61.1% of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e concurrently carried the \u003cem\u003etet(A)\u003c/em\u003e gene, known to result in reduced susceptibility to tigecycline, signaling a need for cautious use of tigecycline in treating such strains [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Additionally, a significant 14.0% of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e harbored the \u003cem\u003emcr\u003c/em\u003e1.1 gene, a horizontally transmitted colistin resistance gene [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This finding is of great concern as it poses a challenge to the effectiveness of colistin in treating infections caused by these strains. Further complicating matters, our study identified nine derivatives of \u003cem\u003emcr\u003c/em\u003e (\u003cem\u003emcr-2\u003c/em\u003e to \u003cem\u003emcr-10\u003c/em\u003e) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], suggesting a potential reduction in polymyxin sensitivity among \u003cem\u003ebla\u003c/em\u003eNDM-positive strains due to the widespread presence of \u003cem\u003emcr\u003c/em\u003e. Furthermore, 46.6% of \u003cem\u003ebla\u003c/em\u003eNDM-positive strains simultaneously carried the Trimethoprim-resistance gene \u003cem\u003edfrA12\u003c/em\u003e and Florfenicol resistance genes \u003cem\u003efloR\u003c/em\u003e, indicating a multi-drug resistance profile. Notably, in strains carrying both \u003cem\u003emcr-1\u003c/em\u003e and \u003cem\u003ebla\u003c/em\u003eNDM-5, our study revealed IncFIB as the main plasmid carrying both genes, deviating from previous observations [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], possibly due to the extensive inclusion of strains in our analysis. This emphasizes the intricate interplay of resistance mechanisms and highlights the necessity for vigilant antimicrobial management strategies.\u003c/p\u003e \u003cp\u003eST analysis revealed a diverse array of STs among \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e. Notably, ST167 dominated in China and India, while ST361 was predominant in Europe, diverging from previous reports which indicated that ST101 and ST131 are the most prevalent clones in Asia, ST101 and ST405 are the dominant STs in Europe [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This discrepancy may arise from the focus on \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e in our study, reflecting distinct strain compositions. Consistent with other studies, ST167 and ST410 emerged as international epidemic clones linked with \u003cem\u003ebla\u003c/em\u003eNDM-5 [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Contrary to these findings, no specific ST linkage was observed for \u003cem\u003ebla\u003c/em\u003eNDM-1[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], although some strains were assigned to ST410, ST156, ST167, ST10, and ST101. Remarkably, ST13, recognized as the pandemic clone associated with global dissemination of the \u003cem\u003ebla\u003c/em\u003eCTX-M-15 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], was identified in only 17 \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e isolates, underscoring a divergence in the dissemination patterns of different ARGs.\u003c/p\u003e \u003cp\u003eAmong various VFs, over half of the strains carried \u003cem\u003eterC\u003c/em\u003e, \u003cem\u003egad\u003c/em\u003e, \u003cem\u003etraT\u003c/em\u003e, and \u003cem\u003eiss\u003c/em\u003e. \u003cem\u003eterC\u003c/em\u003e, encoding a tellurium iron resistance protein [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The \u003cem\u003egad\u003c/em\u003e gene, facilitating survival in acidic environments, and the \u003cem\u003etraT\u003c/em\u003e gene, which encodes protections, along with \u003cem\u003eiss\u003c/em\u003e, \u003cem\u003esitA\u003c/em\u003e, and \u003cem\u003ehra\u003c/em\u003e genes being associated with urinary tract infection, were also prevalent [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Importantly, the distribution of predominant VFs varied significantly among the prevailing clones, highlighting the intricate relationship between genetic backgrounds and virulence traits [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIncFII and IncFIB emerged as the predominant plasmids in all \u003cem\u003ebla\u003c/em\u003eNDM-carrying isolates, showcasing a correlation with the \u003cem\u003emph(A)\u003c/em\u003e and \u003cem\u003etra(T)\u003c/em\u003e genes. Following closely were IncX3 and IncFIA. Notably, it\u0026rsquo;s reported that IncX3-type plasmids are recognized as key contributors to horizontal transmission of \u003cem\u003ebla\u003c/em\u003eNDM in CREC [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and IncFIB is prevalent especially in \u003cem\u003ebla\u003c/em\u003eNDM-1-carrying \u003cem\u003eE. coli\u003c/em\u003e in Greece [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Serotype O101, associated with both animal and human diseases, is commonly detected among pathogenic \u003cem\u003eE. coli\u003c/em\u003e [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In our study, O101:H9 emerged as the most prevalent, even though reports of this specific serotype are limited. Interestingly, O101:H9 has been linked to possible international dissemination via migratory birds [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], emphasizing the importance of employing techniques such as multiplex PCR or whole-genome sequencing that go beyond focusing solely on serotype O157:H7 in clinical laboratories. These diverse molecular findings underscore the necessity for ongoing surveillance of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e strains.\u003c/p\u003e \u003cp\u003eTo our best knowledge, this study represents the largest comprehensive report on the prevalence and genetic characterization of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e worldwide, utilizing whole-genome data. However, it is crucial to acknowledge certain limitations. Firstly, the inclusion criteria were limited to data available on the NCBI database, potentially introducing selection bias. Secondly, the study's ability to fully capture the global prevalence of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e is constrained by the insufficient availability of genome data from many countries. Thirdly, the absence of detailed epidemiological data limits the exploration of factors such as prior exposure to healthcare settings and environmental influences, which may play a significant role in the global transmission of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e. Despite these limitations, this study offers valuable insights into the epidemiology and genomic characteristics of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e on a global scale.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study offers a comprehensive understanding of the prevalence, genetic diversity, and associated factors of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e, submitted by 43 countries over the period 2003\u0026ndash;2022. \u003cem\u003ebla\u003c/em\u003eNDM-5 is the predominant variant, identified in diverse ST and O:H serotypes, highlighting the complexity and adaptability of these multidrug-resistant strains. The study delves into the intricate relationship between plasmid types, virulence factors, and ARGs, providing valuable insights for clinical treatment and public health interventions. As the global threat of antimicrobial resistance continues to escalate, this study serves as a critical resource for guiding future research, surveillance, and implementation of effective strategies to address the challenges posed by \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e. The findings underscore the urgent need for sustained global collaboration, surveillance efforts, and antimicrobial stewardship to mitigate the impact of these highly resistant strains on public health.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable (All the data were downloaded from NCBI database).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our gratitude to everyone who participated in this research study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in this study are included in this article/Supplementary material, further inquiries can be directed to the corresponding authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Affiliations\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eDepartment of Laboratory Medicine, Peking University First Hospital, Beijing, China\u003c/p\u003e\n\u003cp\u003eDepartment of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Jiangsu, China\u003c/p\u003e\n\u003cp\u003eClinical Research Center, the Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, China\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXC contributed to the experimental design of the study. CX, RY, JZ, JZ and XC performed data acquisition and statistical analysis. CX, RY and XC performed bioinformatics analysis and writing. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to\u0026nbsp;Xiaoli Cao.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the National Natural Science Foundation of China (81902124).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, et al. 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Zool Res. 2021;42(4):461\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.24272/j.issn.2095-8137.2021.153\u003c/span\u003e\u003cspan address=\"10.24272/j.issn.2095-8137.2021.153\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-clinical-microbiology-and-antimicrobials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cmam","sideBox":"Learn more about [Annals of Clinical Microbiology and Antimicrobials](http://ann-clinmicrob.biomedcentral.com/)","snPcode":"12941","submissionUrl":"https://submission.nature.com/new-submission/12941/3","title":"Annals of Clinical Microbiology and Antimicrobials","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Carbapenem-resistant Escherichia coli, blaNDM, Serotype, Virulence factors, Sequence types","lastPublishedDoi":"10.21203/rs.3.rs-3955970/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3955970/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e \u003cem\u003eEscherichia. coli\u003c/em\u003e is the most frequent host for New Delhi metallo-β-lactamase (NDM) which hydrolyzes almost all β-lactams except aztreonam. The worldwide spread of \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e heavily threatens public health.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed to explore the global genomic epidemiology of \u003cem\u003ebla\u003c/em\u003eNDM- carrying \u003cem\u003eE. coli\u003c/em\u003e isolates, providing information for preventing the dissemination of such strains.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eGlobal \u003cem\u003eE. coli\u003c/em\u003e genomes were downloaded from NCBI database and \u003cem\u003ebla\u003c/em\u003eNDM was detected using BLASTP. Per software was used to extract meta information on hosts, resources, collection data, and countries of origin from GenBank. The sequence types (STs) and distribution of antimicrobial resistance gene (ARG) were analyzed by CLC Workbench; Plasmid replicons, serotypes and virulence genes (VFs) were analyzed by submitting the genomes to the websites. Statistical analyses were performed to access the relationships among ARGs and plasmid replicons.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eUntil March 2023, 1,774 out of 33,055 isolates collected during 2003\u0026ndash;2022 were found to contain \u003cem\u003ebla\u003c/em\u003eNDM in total. Among them, 15 \u003cem\u003ebla\u003c/em\u003eNDM variants were found with \u003cem\u003ebla\u003c/em\u003eNDM-5 (74.1%) being most frequent, followed by \u003cem\u003ebla\u003c/em\u003eNDM-1 (16.6%) and \u003cem\u003ebla\u003c/em\u003eNDM-9 (4.6%). Among the 213 ARGs identified, 27 \u003cem\u003ebla\u003c/em\u003eCTX-M and 39 \u003cem\u003ebla\u003c/em\u003eTEM variants were found with \u003cem\u003ebla\u003c/em\u003eCTX-M-15 (n\u0026thinsp;=\u0026thinsp;438, 24.7%) and \u003cem\u003ebla\u003c/em\u003eTEM-1B (n\u0026thinsp;=\u0026thinsp;1092, 61.6%) being the most frequent ones, respectively. In addition, 546 (30.8%) plasmids mediated \u003cem\u003eampC\u003c/em\u003e genes, 508 (28.6%) exogenously acquired 16S rRNA methyltransferase encoding genes and 262 (14.8%) \u003cem\u003emcr\u003c/em\u003e were also detected. Among the 232 distinct STs, ST167 (17.2%) were the most prevalent. As for plasmids, more than half of isolates contained IncFII, IncFIB and IncX3. The VF \u003cem\u003eterC\u003c/em\u003e, \u003cem\u003egad\u003c/em\u003e, \u003cem\u003etraT\u003c/em\u003e and \u003cem\u003eiss\u003c/em\u003e as well as the serotypes O101:H9 (n\u0026thinsp;=\u0026thinsp;231, 13.0%), O8:H9 (n\u0026thinsp;=\u0026thinsp;115, 6.5%) and O9:H30 (n\u0026thinsp;=\u0026thinsp;99, 5.6%) were frequently observed.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe study delves into the intricate relationship between plasmid types, virulence factors, and ARGs, which provides valuable insights for clinical treatment and public health interventions, and serves as a critical resource for guiding future research, surveillance, and implementation of effective strategies to address the challenges posed by \u003cem\u003ebla\u003c/em\u003eNDM-carrying \u003cem\u003eE. coli\u003c/em\u003e. The findings underscore the urgent need for sustained global collaboration, surveillance efforts, and antimicrobial stewardship to mitigate the impact of these highly resistant strains on public health.\u003c/p\u003e","manuscriptTitle":"Epidemiological and genomic characteristics of global blaNDM-carrying Escherichia coli","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-16 11:45:23","doi":"10.21203/rs.3.rs-3955970/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2024-06-15T12:55:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-10T09:39:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"72265673534689726100594184445392407808","date":"2024-06-10T09:34:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-03T20:14:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"315057967876002497658279935872538615216","date":"2024-05-25T19:15:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"d21f3f8a-e4fc-4bb4-8476-ce8e038c86c3","date":"2024-03-05T10:48:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-04T06:09:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-03T11:19:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-15T07:26:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Clinical Microbiology and Antimicrobials","date":"2024-02-14T11:33:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-clinical-microbiology-and-antimicrobials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cmam","sideBox":"Learn more about [Annals of Clinical Microbiology and Antimicrobials](http://ann-clinmicrob.biomedcentral.com/)","snPcode":"12941","submissionUrl":"https://submission.nature.com/new-submission/12941/3","title":"Annals of Clinical Microbiology and Antimicrobials","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a886b472-f789-42bb-a3f1-eb6acf0c8fc1","owner":[],"postedDate":"February 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-06-22T00:29:04+00:00","versionOfRecord":{"articleIdentity":"rs-3955970","link":"https://doi.org/10.1186/s12941-024-00719-x","journal":{"identity":"annals-of-clinical-microbiology-and-antimicrobials","isVorOnly":false,"title":"Annals of Clinical Microbiology and Antimicrobials"},"publishedOn":"2024-06-21 00:29:04","publishedOnDateReadable":"June 21st, 2024"},"versionCreatedAt":"2024-02-16 11:45:23","video":"","vorDoi":"10.1186/s12941-024-00719-x","vorDoiUrl":"https://doi.org/10.1186/s12941-024-00719-x","workflowStages":[]},"version":"v1","identity":"rs-3955970","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3955970","identity":"rs-3955970","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}