Nanomotion technology for testing azithromycin susceptibility ofSalmonella enterica

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Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Nanomotion technology for testing azithromycin susceptibility of Salmonella enterica View ORCID Profile Mariliis Hinnu , Toomas Mets , Ivana Kerkez , Marta Putrinš , View ORCID Profile Niilo Kaldalu , Gino Cathomen , Marta Pla Verge , Danuta Cichocka , View ORCID Profile Alexander Sturm , View ORCID Profile Tanel Tenson , ERADIAMR consortium doi: https://doi.org/10.1101/2024.09.05.611511 Mariliis Hinnu 1 Institute of Technology, University of Tartu , Tartu, Estonia Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mariliis Hinnu For correspondence: mariliis.hinnu{at}ut.ee Toomas Mets 1 Institute of Technology, University of Tartu , Tartu, Estonia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ivana Kerkez 1 Institute of Technology, University of Tartu , Tartu, Estonia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marta Putrinš 1 Institute of Technology, University of Tartu , Tartu, Estonia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Niilo Kaldalu 1 Institute of Technology, University of Tartu , Tartu, Estonia Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Niilo Kaldalu Gino Cathomen 2 Resistell AG , Muttenz, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marta Pla Verge 2 Resistell AG , Muttenz, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Danuta Cichocka 2 Resistell AG , Muttenz, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alexander Sturm 2 Resistell AG , Muttenz, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alexander Sturm Tanel Tenson 1 Institute of Technology, University of Tartu , Tartu, Estonia Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Tanel Tenson Abstract Full Text Info/History Metrics Preview PDF ABSTRACT Azithromycin is used to treat invasive salmonellosis, despite conflicting effective concentrations in vitro and in vivo . Resistance of Salmonella enterica to azithromycin is increasing. We demonstrate that nanomotion technology can be used for rapid phenotypic testing of Salmonella ’s susceptibility to azithromycin. Nanomotion changes under various culture conditions correlated with susceptibility measured by MIC determination, CFU counting, and fluorescent reporter-based estimates of intrabacterial azithromycin accumulation. MAIN Invasive salmonellosis caused by Salmonella enterica subspecies is a major threat to human health affecting >20 million people yearly ( 1 , 2 ). Antimicrobial resistance to traditional drugs, such as beta-lactams and fluoroquinolones, has emerged in all invasive S. enterica serovars ( 1 ). The macrolide azithromycin (AZI) has been effectively used to treat Salmonella infections resistant to other drug classes ( 3 – 5 ). AZI remains effective in vivo , despite recommended doses achieving peak serum concentrations in the range of 0.4 μg/ml ( 6 ): 20-fold lower than the MICs for most clinical strains (8 μg/ml) ( 7 ). Resistance to AZI is increasing ( 8 , 9 ), underlining the need for rapid susceptibility testing. Nanomotion technology can be used as a rapid phenotypic antimicrobial susceptibility test (AST) ( 10 – 14 ). The technology is based on measuring oscillations caused by metabolically active organisms attached to a nanomechanical sensor, a cantilever ( 11 , 15 ). The classification into resistant/susceptible categories is based on machine learning algorithms for specific strain-drug combinations. The susceptibility phenotype can already be detected two hours after blood culture positivity ( 14 ). The technology has been successfully applied in various bacterial species, and two clinical studies have been concluded (NANO-RAST ( 16 ), NCT05002413 ) and PHENOTECH- 1 ( 14 ), NCT05613322 ). Prior to this study, nanomotion had not been used to determine susceptibility to AZI or any other macrolide. We recorded nanomotion of S. enterica under various experimental conditions affecting its susceptibility to AZI. We used neutral and acidic media, and two different incubation temperatures. In the early stages of development, nanomotion was measured at ambient room temperature (RT). The current setup uses 37°C for all ASTs to mimic physiological conditions in humans and to decrease the time to results ( 14 ). Based on MIC values, Salmonella is up to 4 times more sensitive to AZI at RT compared to 37°C in different growth media (Fig. S1A; Table S1). This effect cannot be fully explained by the differences in growth rates (Fig. S1B). Nanomotion was recorded for AZI-susceptible S. enterica serovar Typhimurium SL1344 ( 17 – 19 ) (wild-type; wt) during AZI treatment and subsequent recovery in fresh drug-free medium at both RT and 37°C ( Fig. 1 & S2). Before the addition of the antibiotic, nanomotion variance over time increased, indicating the presence and physiological activity of live bacteria on the cantilever. In the untreated sample, the signal continued to increase during the measurement ( Fig. 1A ). When AZI was added at concentrations exceeding the MIC, the nanomotion signal slope decreased. After removal of AZI nanomotion started to increase again in fresh drug-free medium at 37°C, indicating recovery ( Fig. 1C ; S2). However, no recovery was observed when the experiments were conducted at RT ( Fig. 1B ; S2), except after treatment with 16 μg/ml AZI (Fig. S2). In all cases, bacteria remained on the cantilever at the end of the experiment (Fig. S3). Download figure Open in new tab Figure 1. Variance over time of the nanomotion signal measurements of wt Salmonella without AZI (A) or with 128 µg/ml AZI for 2 hours and subsequent recovery in fresh medium at room temperature (RT) (B) or at 37°C (C). Green indicates bacterial nanomotion variance signal before adding the drug, orange is during drug treatment and pink is the recovery in fresh medium after removing the drug. Means ± SEM (N ≥ 3 biological replicates) shown for nanomotion data. D. Recovery of wt Salmonella colonies on LB-agar after 2h of treatment with AZI at indicated temperature at pH 7.4. Grey dotted line indicates the initial inoculum. Means ± SD (N ≥ 3 biological replicates). We hypothesized that the bacteria might have been killed or their recovery delayed. Delay in post-treatment recovery after an antibiotic is removed from the extracellular environment is known as the postantibiotic effect (PAE), and it impacts antibiotic dosing ( 20 , 21 ). Colony counts after treatment indicated that AZI killed less than one log of S. enterica when plates were incubated at 37°C during recovery. However, during RT recovery, the same concentrations of AZI killed at least one log more irrespective of the treatment temperature ( Fig. 1D ). The enhanced post-treatment killing by AZI at a lower temperature may reflect slower dissociation of the drug from the ribosome, which is known to increase the bactericidal activity of macrolides ( 22 ). The slope of the nanomotion variance during drug exposure is a proxy for estimating drug susceptibility ( 14 ). To test whether detection of AZI resistance in Salmonella is feasible with nanomotion, we determined the slope of the variance at different AZI concentrations for wt SL1344 and a resistant mutant acrB R717Q, which harbors a clinically relevant mutation that increases AZI efflux in the acrAB-TolC efflux pump and has an MIC of 32 μg/ml ( 8 , 23 – 25 ). We also determined the slope of the variance for wt strain at acidic pH, a condition encountered by intracellular Salmonella in acidic vacuoles ( 26 ) which increases AZI’s MIC above 1024 μg/ml (Table S1) ( 18 ). We used the rolling regression method for slope estimation, which demonstrated better reliability and robustness compared to the methods employed in previous studies (Supplementary materials and methods, Figure S4). Remarkable differences in nanomotion arise between the strains at AZI concentrations near the MIC value of the wt at neutral pH. The drug slope values of the resistant mutant begin decreasing at higher AZI concentrations than the wt ( Fig. 2A ). A comparable difference is seen in the wt between neutral and acidic pH ( Fig. 2B ), indicating that nanomotion can be used to detect AZI susceptibility. Download figure Open in new tab Figure 2. The drug-phase slope of nanomotion variance reflects the response to AZI in Salmonella and can be used to estimate susceptibility to the drug. A. The slope of the variance during the drug phase of the AZI-resistant acrB R717Q mutant and susceptible wild-type (wt) strain SL1344 at neutral pH. B. Drug slope of the wt strain at two different pH values. RT data; means ± SEM (N≥3); transparent data points shown, where N <3. *Indicates p-value <0.05 of the difference between the groups at the indicated concentration. Drug slopes started to decline at AZI concentrations several-fold below the MIC, indicating an effect on the bacteria ( Fig 2 ). To verify these sub-MIC effects of AZI, we used a fluorescent reporter in which the translational attenuation-based regulatory leader region ( ermCL ) is fused to GFP ( Fig. 3A ) instead of the native ermC methyltransferase that confers macrolide resistance ( 27 , 28 ). Macrolides stall the ribosome during ErmCL translation, which opens the mRNA secondary structure allowing translation initiation of the downstream gene ( 28 ). AZI induced GFP expression in bacteria containing the reporter plasmid in a concentration-dependent manner ( Fig. 3B ) at these same sub-MIC concentrations where drug slopes began to decline. Maximum reporter induction was observed at or slightly above the MIC at pH 7.4, however little to no induction was seen at concentrations ≤1 µg/ml (Fig.-s 3B, S5-S6), which is in good agreement with the nanomotion data ( Fig. 2 ). In accordance with the lower MIC at RT, the signal peaked at 4X lower concentrations at RT than it did at 37°C ( Fig. 3B , S6). However, the induction levels remained significantly lower at RT, reflecting slower translation processes. At pH 5.5, GFP induction began at significantly higher concentrations compared to pH 7.4 (Fig.-s 3B, S5-S6), supporting the notion that the pH-dependence of AZI sensitivity is due to differences in antibiotic accumulation within the cell. AZI did not induce GFP at RT at pH 5.5 ( Fig. 3B , S6). Download figure Open in new tab Figure 3. ErmCL-based reporter system was used to estimate AZI’s intracellular concentrations and effects on translation. A. Schematic representation of the reporter system. B. GFP induction of wt Salmonella after 2 h treatment with AZI. Flow cytometry data. Means ± SD (N=3). In summary, we show that nanomotion technology can be used for rapid detection of AZI susceptibility. MIC values obtained using the standard dilution method, CFU counting results, and ermCL -dependent GFP induction by AZI were all consistent with the physiological responses recorded by nanomotion. Additionally, we found that nanomotion is effective for detecting PAE and assessing bactericidal activity. Our study highlights the importance of assay conditions, which significantly affected AZI efficacy and readout of the test. Author contributions M.H. - investigation, methodology, data curation, formal analysis, visualization, writing - original draft; T.M., I.K., M.P.V. - investigation; G.C. - data curation, formal analysis, software; M.P., D.C., A.S., N.K., T.T. - conceptualization, funding acquisition, project administration, supervision. All authors contributed to the review & editing of the manuscript. Resistell AG has developed the patented (WO2023174728A1) methodology for nanomotion detection. Conflicts of interest G.C., M.P.V., D.C., and A.S. are employees of Resistell AG and declare competing financial interests. Acknowledgements This research was funded by Estonian Research Council grants PRG335 and MOB3ERA7 Effective RApid DIagnostics and treatment of AntiMicrobial Resistant bacteria (ERADIAMR), and EU TWINNING project “Molecular Infection Biology Estonia – Research Capacity Building” (H2020-WIDESPREAD-2018-2020/GA: 857518). We are thankful to Dorota Klepacki and Alexander Mankin (University of Illinois at Chicago) for preparing and sharing the reporter. We are thankful to the whole Resistell team for helping with the nanomotion experiments. Footnotes ↵ § The ERADIAMR (Effective RApid DIagnostics and treatment of AntiMicrobial Resistant bacteria) is a European project on antimicrobial resistance part of the JPI-AMR action. The ERADIAMR consortium is composed of the following persons: - Christèle Aubry, Amanda Luraschi-Eggemann, Maria Georgevia & Gilbert Greub, Université de Lausanne, Switzerland - Gino Cathomen, Danuta Cichocka & Alexander Sturm, Resistell AG, Muttenz, Switzerland - Maria Garcia-Castillo & Rafael Canton, Hospital Ramón y Cajal-IRYCIS and CIBER de Enfermedades Infecciosas (CIBERINFEC). Madrid, Spain - Nicolas Oswaldo Trinler & Susanne Häussler, Helmholtz Centre for Infection Research, Germany - Mariliis Hinnu, Niilo Kaldalu & Tanel Tenson, Institute of Technology, University of Tartu, Estonia - Tailise de Souza Guerreiro Rodrigues & Stefano Pagliara, Living Systems Institute, University of Exeter, UK References 1. ↵ Crump JA , Sjölund-Karlsson M , Gordon MA , Parry CM . 2015 . Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections . Clin Microbiol Rev 28 : 901 – 937 . OpenUrl Abstract / FREE Full Text 2. ↵ Marks F , von Kalckreuth V , Aaby P , Adu-Sarkodie Y , El Tayeb MA , Ali M , Aseffa A , Baker S , Biggs HM , Bjerregaard-Andersen M , Breiman RF , Campbell JI , Cosmas L , Crump JA , Espinoza LMC , Deerin JF , Dekker DM , Fields BS , Gasmelseed N , Hertz JT , Van Minh Hoang N , Im J , Jaeger A , Jeon HJ , Kabore LP , Keddy KH , Konings F , Krumkamp R , Ley B , Løfberg SV , May J , Meyer CG , Mintz ED , Montgomery JM , Niang AA , Nichols C , Olack B , Pak GD , Panzner U , Park JK , Park SE , Rabezanahary H , Rakotozandrindrainy R , Raminosoa TM , Razafindrabe TJL , Sampo E , Schütt-Gerowitt H , Sow AG , Sarpong N , Seo HJ , Sooka A , Soura AB , Tall A , Teferi M , Thriemer K , Warren MR , Yeshitela B , Clemens JD , Wierzba TF . 2017 . Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study . Lancet Glob Health 5 : e310 – e323 . OpenUrl 3. ↵ Butler T , Frenck RW , Johnson RB , Khakhria R. 2001 . In vitro effects of azithromycin on Salmonella typhi: early inhibition by concentrations less than the MIC and reduction of MIC by alkaline pH and small inocula . J Antimicrob Chemother 455–458 . 4. Dolecek C , Tran TPL , Nguyen NR , L. Tp , Ha V , Phung QT , Doan CD , Nguyen TBB , Duong TL , Luong BH , Nguyen TB , Nguyen TAH , Pham ND , Mai NL , Phan VBB , Vo AH , Nguyen VMH , Tran TTN , Tran TC , Schultsz C , Dunstan SJ , Stepniewska K , Campbell JI , To SD , Basnyat B , Nguyen VVC , Nguyen VS , Nguyen TC , Tran TH , Farrar J. 2008 . A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam . PloS One 3 : e2188 . OpenUrl CrossRef PubMed 5. ↵ DuPont HL . 2009 . Bacterial Diarrhea . N Engl J Med 361 : 1560 – 1569 . OpenUrl CrossRef PubMed Web of Science 6. ↵ Foulds G , Shepard RM , Johnson RB . 1990 . The pharmacokinetics of azithromycin in human serum and tissues . J Antimicrob Chemother 25 : 73 – 82 . OpenUrl CrossRef PubMed Web of Science 7. ↵ Parry CM , Thieu NTV , Dolecek C , Karkey A , Gupta R , Turner P , Dance D , Maude RR , Ha V , Tran CN , Thi PL , Van Be BP , Phi LTT , Ngoc RN , Ghose A , Dongol S , Campbell JI , Thanh DP , Thanh TH , Moore CE , Sona S , Gaind R , Deb M , Van Anh H , Van SN , Tinh HT , Day NPJ , Dondorp A , Thwaites G , Faiz MA , Phetsouvanh R , Newton P , Basnyat B , Farrar JJ , Bakera S. 2015 . Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A . Antimicrob Agents Chemother 59 : 2756 – 2764 . OpenUrl Abstract / FREE Full Text 8. ↵ Sajib MSI , Tanmoy AM , Hooda Y , Rahman H , Andrews JR , Garrett DO , Endtz HP , Saha SK , Saha S. 2021 . Tracking the Emergence of Azithromycin Resistance in Multiple Genotypes of Typhoidal Salmonella . mBio 12 . 9. ↵ Jabeen K , Saleem S , Nizamuddin S , Arshad F , Jahan S , Hasnain F , Tariq W , Tahir MJ , Yousaf Z , Asghar MS . 2023 . Reporting of Azithromycin Activity against Clinical Isolates of Extensively Drug-Resistant Salmonella enterica Serovar Typhi doi: 10.4269/ajtmh.22-0557 . OpenUrl CrossRef 10. ↵ Lissandrello C , Inci F , Francom M , Paul MR , Demirci U , Ekinci KL . 2014 . Nanomechanical motion of Escherichia coli adhered to a surface . Appl Phys Lett 105 : 113701 . OpenUrl CrossRef PubMed 11. ↵ Longo G , Alonso-Sarduy L , Rio LM , Bizzini A , Trampuz A , Notz J , Dietler G , Kasas S. 2013 . Rapid detection of bacterial resistance to antibiotics using AFM cantilevers as nanomechanical sensors . Nat Nanotechnol 8 : 522 – 526 . OpenUrl CrossRef PubMed 12. Villalba MI , Stupar P , Chomicki W , Bertacchi M , Dietler G , Arnal L , Vela ME , Yantorno O , Kasas S. 2018 . Nanomotion Detection Method for Testing Antibiotic Resistance and Susceptibility of Slow-Growing Bacteria . Small 14 : 1702671 . OpenUrl CrossRef 13. Vocat A , Sturm A , Jóźwiak G , Cathomen G , Świątkowski M , Buga R , Wielgoszewski G , Cichocka D , Greub G , Opota O. 2023 . Nanomotion technology in combination with machine learning: a new approach for a rapid antibiotic susceptibility test for Mycobacterium tuberculosis . Microbes Infect 25 : 105151 . OpenUrl 14. ↵ Sturm A , Jóźwiak G , Verge MP , Munch L , Cathomen G , Vocat A , Luraschi-Eggemann A , Orlando C , Fromm K , Delarze E , Świątkowski M , Wielgoszewski G , Totu RM , García-Castillo M , Delfino A , Tagini F , Kasas S , Lass-Flörl C , Gstir R , Cantón R , Greub G , Cichocka D. 2024 . Accurate and rapid antibiotic susceptibility testing using a machine learning-assisted nanomotion technology platform . Nat Commun 15 : 2037 . OpenUrl 15. ↵ Kasas S , Ruggeri FS , Benadiba C , Maillard C , Stupar P , Tournu H , Dietler G , Longo G. 2015 . Detecting nanoscale vibrations as signature of life . Proc Natl Acad Sci 112 : 378 – 381 . OpenUrl Abstract / FREE Full Text 16. ↵ Caruana G , Kritikos A , Vocat A , Luraschi A , Delarze E , Sturm A , Verge MP , Jozwiak G , Kushwaha S , Delaloye J , Cichocka D , Greub G. 2022 . Investigating nanomotion-based technology (Resistell AST) for rapid antibiotic susceptibility testing among adult patients admitted to a tertiary-care hospital with Gram-negative bacteraemia: protocol for a prospective, observational, cross-sectional, single-arm study . BMJ Open 12 : e064016 . OpenUrl Abstract / FREE Full Text 17. ↵ Claudi B , Spröte P , Chirkova A , Personnic N , Zankl J , Schürmann N , Schmidt A , Bumann D. 2014 . Phenotypic variation of salmonella in host tissues delays eradication by antimicrobial chemotherapy . Cell 158 : 722 – 733 . OpenUrl CrossRef PubMed Web of Science 18. ↵ Hinnu M , Putrinš M , Kogermann K , Bumann D , Tenson T. 2022 . Making Antimicrobial Susceptibility Testing More Physiologically Relevant with Bicarbonate? Antimicrob Agents Chemother 66 . 19. ↵ Hoiseth SK , Stocker B a. D. 1981 . Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. 5812 . Nature 291 : 238 – 239 . OpenUrl CrossRef PubMed Web of Science 20. ↵ Gilbert DN . 1991 . Once-daily aminoglycoside therapy . Antimicrob Agents Chemother 35 : 399 – 405 . OpenUrl Abstract / FREE Full Text 21. ↵ ter Braak EW , de Vries PJ , Bouter KP , van der Vegt SG , Dorrestein GC , Nortier JW , van Dijk A , Verkooyen RP , Verbrugh HA . 1990 . Once-daily dosing regimen for aminoglycoside plus β-Lactam combination therapy of serious bacterial infections: Comparative trial with netilmicin plus ceftriaxone . Am J Med 89 : 58 – 66 . OpenUrl CrossRef PubMed Web of Science 22. ↵ Svetlov MS , Vázquez-Laslop N , Mankin AS . 2017 . Kinetics of drug–ribosome interactions defines the cidality of macrolide antibiotics . Proc Natl Acad Sci 114 : 13673 – 13678 . OpenUrl Abstract / FREE Full Text 23. ↵ Hooda Y , Sajib MSI , Rahman H , Luby SP , Bondy-Denomy J , Santosham M , Andrews JR , Saha SK , Saha S. 2019 . Molecular mechanism of azithromycin resistance among typhoidal Salmonella strains in Bangladesh identified through passive pediatric surveillance . PLoS Negl Trop Dis 13 . 24. Trampari E , Prischi F , Vargiu AV , Abi-Assaf J , Bavro VN , Webber MA . 2023 . Functionally distinct mutations within AcrB underpin antibiotic resistance in different lifestyles . Npj Antimicrob Resist 1 : 1 – 13 . OpenUrl CrossRef 25. ↵ Zwama M , Nishino K. 2022 . Proximal Binding Pocket Arg717 Substitutions in Escherichia coli AcrB Cause Clinically Relevant Divergencies in Resistance Profiles . Antimicrob Agents Chemother 66 : e0239221 . OpenUrl 26. ↵ Kenney LJ . 2019 . The role of acid stress in Salmonella pathogenesis . Curr Opin Microbiol 47 : 45 – 51 . OpenUrl CrossRef 27. ↵ Aleksandrova EV , Ma C-X , Klepacki D , Alizadeh F , Vázquez-Laslop N , Liang J-H , Polikanov YS , Mankin AS . 2024 . Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms . Nat Chem Biol 1–11 . 28. ↵ Gupta P , Kannan K , Mankin AS , Vázquez-Laslop N. 2013 . Regulation of Gene Expression by Macrolide-Induced Ribosomal Frameshifting . Mol Cell 52 : 629 – 642 . OpenUrl CrossRef PubMed Web of Science View the discussion thread. Back to top Previous Next Posted September 06, 2024. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Share Nanomotion technology for testing azithromycin susceptibility of Salmonella enterica Mariliis Hinnu , Toomas Mets , Ivana Kerkez , Marta Putrinš , Niilo Kaldalu , Gino Cathomen , Marta Pla Verge , Danuta Cichocka , Alexander Sturm , Tanel Tenson , ERADIAMR consortium bioRxiv 2024.09.05.611511; doi: https://doi.org/10.1101/2024.09.05.611511 Share This Article: Copy Citation Tools Nanomotion technology for testing azithromycin susceptibility of Salmonella enterica Mariliis Hinnu , Toomas Mets , Ivana Kerkez , Marta Putrinš , Niilo Kaldalu , Gino Cathomen , Marta Pla Verge , Danuta Cichocka , Alexander Sturm , Tanel Tenson , ERADIAMR consortium bioRxiv 2024.09.05.611511; doi: https://doi.org/10.1101/2024.09.05.611511 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Microbiology Subject Areas All Articles Animal Behavior and Cognition (7649) Biochemistry (17737) Bioengineering (13925) Bioinformatics (42059) Biophysics (21495) Cancer Biology (18643) Cell Biology (25576) Clinical Trials (138) Developmental Biology (13405) Ecology (19946) Epidemiology (2067) Evolutionary Biology (24370) Genetics (15626) Genomics (22551) Immunology (17769) Microbiology (40480) Molecular Biology (17209) Neuroscience (88782) Paleontology (667) Pathology (2843) Pharmacology and Toxicology (4835) Physiology (7662) Plant Biology (15177) Scientific Communication and Education (2047) Synthetic Biology (4304) Systems Biology (9838) Zoology (2272)