Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria

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However, there is limited comparative information on the antibiotic resistance genes (ARGs) and mechanisms across the Pseudomonas pathogenic groups. Methods: The complete genomes of five Pseudomonas pathogen groups, P. aeruginosa, P. fluorescens, P. putida, P. stutzeri and P. syringae, were analyzed for ARGs. Results: A significant number of ARGs were identified in the P. aeruginosa genome compared to the other Pseudomonas pathogens. The opportunistic pathogens P. stutzeri and P. putida were shown to be the closest to P. aeruginosa with an average nucleotide identity (%) of 80.30 and 79.52. The pathogen genome with the least hit was P. stutzeri. The four major antibiotic resistance mechanisms that include the efflux, inactivation, target alteration and efflux::target alteration were reported. Conclusion: The findings of this brief report could be useful in understanding the chemotherapeutics against antibiotic resistance strains of Pseudomonas pathogens" } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/9-903/v1", "name": "Genome-wide analyses reveal antibiotic resistance genes and mechanisms..." } } ] } Home Browse Genome-wide analyses reveal antibiotic resistance genes and mechanisms... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Benson O. Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.12688/f1000research.25391.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Brief Report Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] Otarigho Benson https://orcid.org/0000-0001-6347-3831 Otarigho Benson https://orcid.org/0000-0001-6347-3831 PUBLISHED 04 Aug 2020 Author details Author details Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, 97239, USA Otarigho Benson Roles: Conceptualization, Data Curation, Formal Analysis, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Pathogens gateway. This article is included in the Antimicrobial Resistance collection. Abstract Background: The global emergence and re-emergence of antibiotic resistance among the Pseudomonas pathogens causes great problems to patients undergoing chemotherapy. However, there is limited comparative information on the antibiotic resistance genes (ARGs) and mechanisms across the Pseudomonas pathogenic groups. Methods: The complete genomes of five Pseudomonas pathogen groups, P. aeruginosa , P. fluorescens , P. putida , P. stutzeri and P. syringae , were analyzed for ARGs. Results: A significant number of ARGs were identified in the P. aeruginosa genome compared to the other Pseudomonas pathogens. The opportunistic pathogens P. stutzeri and P. putida were shown to be the closest to P. aeruginosa with an average nucleotide identity (%) of 80.30 and 79.52. The pathogen genome with the least hit was P. stutzeri . The four major antibiotic resistance mechanisms that include the efflux, inactivation, target alteration and efflux::target alteration were reported. Conclusion: The findings of this brief report could be useful in understanding the chemotherapeutics against antibiotic resistance strains of Pseudomonas pathogens READ ALL READ LESS Keywords Pseudomonas, Antibiotics Resistance, bacterial pathogen, P. aeruginosa Corresponding Author(s) Otarigho Benson ( [email protected] ) Close Corresponding author: Otarigho Benson Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2020 Benson O. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Benson O. Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.12688/f1000research.25391.1 ) First published: 04 Aug 2020, 9 :903 ( https://doi.org/10.12688/f1000research.25391.1 ) Latest published: 04 Aug 2020, 9 :903 ( https://doi.org/10.12688/f1000research.25391.1 ) Introduction The emergence of Gram-negative bacterial antibiotics resistance is a growing threat to antibiotic therapy. The bacterial pathogens in the genus Pseudomonas are mostly opportunistic that cause great damage and loss of life ( Breidenstein et al., 2011 ; Evans et al., 2008 ; Kawai, 1974 ; Lalucat et al., 2006 ). These Pseudomonas pathogens are pervasive that is able to infect, survive and proliferate in a wide range of biotic and abiotic environments ( Azam & Khan, 2019 ; Silby et al., 2011 ). Presently, there are seven groups in the genus Pseudomonas, with P. aeruginosa being the most pathogenic ( Barbier et al., 2013 ) and which causes high morbidity and mortality in cystic fibrosis patients and immunocompromised individuals ( Sadikot et al., 2005 ). The other Pseudomonas pathogenic groups include P. fluorescens ( Biaggini et al., 2015 ) , P. putida ( Fernández et al., 2015 ) , P. stutzeri ( Lalucat et al., 2006 ) and P. syringae ( Xin et al., 2018 ) . P. aeruginosa is the major cause of infections in developed countries due to its highly evolved resistance to a wide variety of antibiotics ( Hancock & Speert, 2000 ) making it very difficult to treat and limiting therapeutics ( Breidenstein et al., 2011 ). Even though P. aeruginosa is the most studied, there are some other Pseudomonas species that exhibits opportunistic pathogenic behavior to animals ( P. fluorescens, P. putida and P. stutzeri ) ( Azam & Khan, 2019 ) and plants ( P. syringae ) ( Xin et al., 2018 ). Most of the known antimicrobial resistance (AMR) gene and mechanistic studies are focused on P. aeruginosa with little attention directed to other Pseudomonas pathogens. Hence, there is need to investigate different Pseudomonas pathogens genomes for diverse antibiotic resistance genes (ARGs) and mechanism. Therefore, this brief report concisely revealed the ARGs, mechanisms and drugs in P. aeruginosa in comparison to other Pseudomonas pathogens. Methods The complete genomes of the five groups of Pseudomonas pathogens, which included the P. aeruginosa ( NC_002516.2 ), P. fluorescens ( NC_016830.1 ), P. putida ( NC_002947.4 ), P. stutzeri ( NC_015740.1 ) and P. syringae ( NC_007005.1 ) fasta file sequences, were downloaded from The National Center for Biotechnology Information Genome database . The five Pseudomonas pathogen genomes were selected to represent the Pseudomonas groups. The fasta file format of the genome sequence of bacteria were thoroughly analyzed for ARGs on the bulk analysis Resistance Gene Identifier (RGI) 5.1.0, CARD 3.0.9 Platform ( Alcock et al., 2020 ) to extract AMR Genes, AMR Gene Family, Drug Class and Resistance Mechanism data. Default select criteria, which identified gene based on strict or perfect only was used. On the RGI platform, each genome sequence file was uploaded and all settings were left at default. The resistance genes, mechanism and drugs obtained from RGI platform were further analyzed using Prism 8 for number of ARG hits, gene family, mechanism and drug class per Pseudomonas species. Results The five Pseudomonas pathogens show significant genome similarity ( Table 1 ). P. stutzeri and P. putida , which have been reported to be opportunist pathogens to humans, were shown to be the closest relations to P. aeruginosa , with an average nucleotide identity (%) of 80.30 and 79.52. P. syringae , which infects plants, had the lowest average nucleotide identity (%) of 78.67. A number of antimicrobial resistance hits and genes were identified across the five Pseudomonas pathogens, but the highest hits were seen in the P. aeruginosa genome. The pathogen genome with the least hit was P. stutzeri ( Figure 1A, B ). The four major antibiotic resistance mechanisms identified were the efflux, inactivation, target alteration and efflux::target alterations in the P. aeruginosa genome. The efflux, inactivation and efflux::target alterations were identified in the P. fluorescens genome, while only the efflux and inactivation alterations were identified in the P. putida , P. stutzeri and P. syringae genomes ( Figure 2A ). The number of drug classes that P. aeruginosa was shown to be resistant to is also shown in Figure 2B . Table 1. Pseudomonas pathogen genomes used in this study. S/N Pseudomonas groups Pathogenic Genome accession No. Average nucleotide identity (%) 1 P. aeruginosa Pathogenic to plants and animals ( Azam & Khan, 2019 ) NC_002516.2 RG 2 P. fluorescens opportunistic human pathogens ( Biaggini et al., 2015 ) NC_016830.1 79.25 3 P. putida opportunistic human pathogens ( Fernández et al., 2015 ) NC_002947.4 79.52 4 P. stutzeri opportunistic human pathogens ( Lalucat et al., 2006 ) NC_015740.1 80.30 5 P. syringae Pathogenic to plants ( Xin et al., 2018 ) NC_007005.1 78.67 Figure 1. P. aeruginosa exhibited more Antibiotics Resistance Genes (ARGs). ( A ) The number of hit per each Pseudomonas pathogen genome ( B ). Number of ARGs per each Pseudomonas pathogen genome. Figure 2. Antibiotic efflux resistance mechanism is widely spread across the Pseudomonas pathogen genome and highly abundant in P. aeruginosa . ( A ) Number of resistance mechanism per each Pseudomonas pathogen genome. ( B ) P. aeruginosa resistance drug class. Drug class key: A= aminoglycoside antibiotic; B= fluoroquinolone antibiotic, diaminopyrimidine antibiotic, phenicol antibiotic; C= macrolide antibiotic, carbapenem, tetracycline antibiotic, acridine dye, diaminopyrimidine antibiotic, phenicol antibiotic; D= macrolide antibiotic, fluoroquinolone antibiotic, aminoglycoside antibiotic, carbapenem, cephalosporin, cephamycin, penam, tetracycline antibiotic, acridine dye, phenicol antibiotic; E= macrolide antibiotic, fluoroquinolone antibiotic, aminoglycoside antibiotic, cephalosporin, penam, tetracycline antibiotic, aminocoumarin antibiotic, diaminopyrimidine antibiotic, phenicol antibiotic; F= macrolide antibiotic, fluoroquinolone antibiotic, cephalosporin, penam, tetracycline antibiotic, aminocoumarin antibiotic, diaminopyrimidine antibiotic, phenicol antibiotic; G= macrolide antibiotic, fluoroquinolone antibiotic, monobactam, carbapenem, cephalosporin, cephamycin, penam, tetracycline antibiotic, peptide antibiotic, aminocoumarin antibiotic, diaminopyrimidine antibiotic, sulfonamide antibiotic, phenicol antibiotic, penem; H= peptide antibiotic; I = phenicol antibiotic; J = sulfonamide antibiotic. Discussion There is an increasing interest and focus in the antibiotic resistance in pathogenic Pseudomonas ( Blair et al., 2014 ; Blanco et al., 2016 ; Li et al., 2015 ; Soto, 2013 ; Webber & Piddock, 2003 ). Hence, this report took advantage of the available Pseudomonas pathogens genomes and analysed for antibiotic resistance genes and mechanisms against different available drugs. The significant number of ARGs and mechanisms were identified in the genome of P. aeruginosa , which is more virulent and well-studied compared to other species. P. aeruginosa also infects a wide range of plants and animals, including humans ( Azam & Khan, 2019 ; Hancock & Speert, 2000 ; Sadikot et al., 2005 ). P. aeruginosa is of great medical importance due to its exhibition of multidrug resistance and its association with serious illnesses ( Breidenstein et al., 2011 ; Evans et al., 2008 ; Gonzalez et al., 2019 ). The most common resistance mechanism of Pseudomonas pathogens is the antibiotic efflux pump mechanism. Although this mechanism is most often seen in P. aeruginosa , it is also found in other Pseudomonas pathogen genomes. It has long been known that the antibiotic efflux pump is a key mechanism of resistance in Gram-negative bacterial pathogens ( Blair et al., 2014 ; Blanco et al., 2016 ; Soto, 2013 ; Webber & Piddock, 2003 ). An antibiotic resistance strain’s efflux pumps allow it to regulate itself by excluding toxic substances, including antimicrobial drugs ( Blair et al., 2014 ; Li et al., 2015 ; Soto, 2013 ; Webber & Piddock, 2003 ). Conclusion The different ARGs and mechanisms against known drugs in P. aeruginosa in comparison to other Pseudomonas pathogen were investigated and concisely reported in this brief report. The findings in this report could be useful in understanding the use of chemotherapeutics against antibiotic-resistant strains of Pseudomonas pathogens. Data availability Source data Table 1 lists the NCBI Genome accession numbers used in this study. Faculty Opinions recommended References Alcock BP, Raphenya AR, Lau TT, et al. : CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res. 2020; 48 (D1): D517–D525. PubMed Abstract | Publisher Full Text | Free Full Text Azam MW, Khan AU: Updates on the pathogenicity status of Pseudomonas aeruginosa . Drug Discov Today. 2019; 24 (1): 350–359. PubMed Abstract | Publisher Full Text Barbier F, Andremont A, Wolff M, et al. : Hospital-acquired pneumonia and ventilator-associated pneumonia: recent advances in epidemiology and management. Curr Opin Pulm Med. 2013; 19 (3): 216–228. PubMed Abstract | Publisher Full Text Biaggini K, Barbey C, Borrel V, et al. : The pathogenic potential of Pseudomonas fluorescens MFN1032 on enterocytes can be modulated by serotonin, substance P and epinephrine. Arch Microbiol. 2015; 197 (8): 983–990. PubMed Abstract | Publisher Full Text Blair JM, Richmond GE, Piddock LJ: Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. Future Microbiol. 2014; 9 (10): 1165–1177. PubMed Abstract | Publisher Full Text Blanco P, Hernando-Amado S, Reales-Calderon JA, et al. : Bacterial multidrug efflux pumps: much more than antibiotic resistance determinants. Microorganisms. 2016; 4 (1): 14. PubMed Abstract | Publisher Full Text | Free Full Text Breidenstein EB, de la Fuente-Núñez C, Hancock RE: Pseudomonas aeruginosa : all roads lead to resistance. Trends Microbiol. 2011; 19 (8): 419–426. PubMed Abstract | Publisher Full Text Evans EA, Kawli T, Tan MW: Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans . PLoS Pathog. 2008; 4 (10): e1000175. PubMed Abstract | Publisher Full Text | Free Full Text Fernández M, Porcel M, de la Torre J, et al. : Analysis of the pathogenic potential of nosocomial Pseudomonas putida strains. Front Microbiol. 2015; 6 : 871. PubMed Abstract | Publisher Full Text | Free Full Text Gonzalez MR, Ducret V, Leoni S, et al. : Pseudomonas aeruginosa zinc homeostasis: Key issues for an opportunistic pathogen. Biochim Biophys Acta Gene Regul Mech. 2019; 1862 (7): 722–733. PubMed Abstract | Publisher Full Text Hancock RE, Speert DP: Antibiotic resistance in Pseudomonas aeruginosa : mechanisms and impact on treatment. Drug Resist Updat. 2000; 3 (4): 247–255. PubMed Abstract | Publisher Full Text Kawai Y: Purification and characterization of pertucin produced by Pseudomonas pertucinogena . Antimicrob Agents Chemother. 1974; 6 (3): 347–359. PubMed Abstract | Publisher Full Text | Free Full Text Lalucat J, Bennasar A, Bosch R, et al. : Biology of Pseudomonas stutzeri . Microbiol Mol Biol Rev. 2006; 70 (2): 510–547. PubMed Abstract | Publisher Full Text | Free Full Text Li XZ, Plésiat P, Nikaido H: The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev. 2015; 28 (2): 337–418. PubMed Abstract | Publisher Full Text | Free Full Text Sadikot RT, Blackwell TS, Christman JW, et al. : Pathogen–host interactions in Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med. 2005; 171 (11): 1209–1223. PubMed Abstract | Publisher Full Text | Free Full Text Silby MW, Winstanley C, Godfrey SA, et al. : Pseudomonas genomes : diverse and adaptable. FEMS Microbiol Rev. 2011; 35 (4): 652–680. PubMed Abstract | Publisher Full Text Soto SM: Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm. Virulence. 2013; 4 (3): 223–229. PubMed Abstract | Publisher Full Text | Free Full Text Webber M, Piddock L: The importance of efflux pumps in bacterial antibiotic resistance. J Antimicrob Chemother. 2003; 51 (1): 9–11. PubMed Abstract | Publisher Full Text Xin XF, Kvitko B, He SY: Pseudomonas syringae : what it takes to be a pathogen. Nat Rev Microbiol. 2018; 16 (5): 316. PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 04 Aug 2020 ADD YOUR COMMENT Comment Author details Author details Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, 97239, USA Otarigho Benson Roles: Conceptualization, Data Curation, Formal Analysis, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 04 Aug 2020, 9:903 https://doi.org/10.12688/f1000research.25391.1 Copyright © 2020 Benson O. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Benson O. Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.12688/f1000research.25391.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 04 Aug 2020 Views 0 Cite How to cite this report: Blanco P. Reviewer Report For: Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.5256/f1000research.28015.r74062 ) The direct URL for this report is: https://f1000research.com/articles/9-903/v1#referee-response-74062 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 Nov 2020 Paula Blanco , Molecular Basis of Adaptation Laboratory, Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.28015.r74062 This brief report deals with the comparison of five Pseudomonas species' genomes in order to get information about the different antibiotic resistance genes and mechanisms. However, the findings described here lack novelty and interest, since the mechanisms of resistance and ... Continue reading READ ALL This brief report deals with the comparison of five Pseudomonas species' genomes in order to get information about the different antibiotic resistance genes and mechanisms. However, the findings described here lack novelty and interest, since the mechanisms of resistance and antimicrobial resistance genes have been widely described in the different Pseudomonas species along the literature. Another point to consider is the number of genomes used for the work. Five complete genomes as a representation of the Pseudomonas pathogens group are not enough for drawing conclusions. It would be much more interesting to take a larger sample of genomes (since they are available) including more than a strain per Pseudomonas species, as well as environmental and clinical strains. A more extensive and careful use of literature should be used along the manuscript, since there are some sentences that does not include a reference. For instance "The most common resistance mechanism of Pseudomonas pathogens is the antibiotic efflux pump mechanism". Also, one of the references for the sentence " P. aeruginosa is of great medical importance due to its exhibition of multidrug resistance and its association with serious illnesses" mention a work performed in the nematode C. elegans . It would be right to include more references related to the clinics. Other aspects of this brief report should need clarification, for instance, what is RG in Table 1? What is the difference between perfect and strict cutoff in Fig1A? Figure 2B also needs clarification, since it is difficult for the reader to make an interpretation and get any conclusion. The author claim in the conclusion that the "findings of this brief report could be useful in understanding the chemotherapeutics against antibiotic resistance strains of Pseudomonas pathogens". However, it is not discussed how actually these data could be used or applied. The author should also mention other similar in silico studies already published to compare his results and give consistency to the methodology employed here. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Antimicrobial resistance evolution I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Blanco P. Reviewer Report For: Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.5256/f1000research.28015.r74062 ) The direct URL for this report is: https://f1000research.com/articles/9-903/v1#referee-response-74062 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Khan AU. Reviewer Report For: Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.5256/f1000research.28015.r68814 ) The direct URL for this report is: https://f1000research.com/articles/9-903/v1#referee-response-68814 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 19 Aug 2020 Asad U. Khan , Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.28015.r68814 Short communication focuses on antibiotic resistance caused by efflux pump overexpression and the use of cryo electron microscopy for protein protein or protein ligand interaction. It also describes the limitations of x ray crystallography. The author also extends the cryo ... Continue reading READ ALL Short communication focuses on antibiotic resistance caused by efflux pump overexpression and the use of cryo electron microscopy for protein protein or protein ligand interaction. It also describes the limitations of x ray crystallography. The author also extends the cryo EM use in interparticle motions of the ribosome in different tRNA bound states, its visualization in various conformations upon the introduction of ribosomal-specific substrates and several bacterial membrane proteins to near atomic resolution. Author successfully explain the utility of structural dynamics in drug designing by identifying important residues through solved structures. However, references are missing from the introduction and targeting efflux pumps to mitigate antibiotic resistance section. May be accepted after minor revision. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? No source data required Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Khan AU. Reviewer Report For: Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.5256/f1000research.28015.r68814 ) The direct URL for this report is: https://f1000research.com/articles/9-903/v1#referee-response-68814 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 04 Aug 2020 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 04 Aug 20 read read Asad U. Khan , Aligarh Muslim University, Aligarh, India Paula Blanco , Universidad Complutense de Madrid, Madrid, Spain Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2020 Blanco P. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Nov 2020 | for Version 1 Paula Blanco , Molecular Basis of Adaptation Laboratory, Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain 0 Views copyright © 2020 Blanco P. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This brief report deals with the comparison of five Pseudomonas species' genomes in order to get information about the different antibiotic resistance genes and mechanisms. However, the findings described here lack novelty and interest, since the mechanisms of resistance and antimicrobial resistance genes have been widely described in the different Pseudomonas species along the literature. Another point to consider is the number of genomes used for the work. Five complete genomes as a representation of the Pseudomonas pathogens group are not enough for drawing conclusions. It would be much more interesting to take a larger sample of genomes (since they are available) including more than a strain per Pseudomonas species, as well as environmental and clinical strains. A more extensive and careful use of literature should be used along the manuscript, since there are some sentences that does not include a reference. For instance "The most common resistance mechanism of Pseudomonas pathogens is the antibiotic efflux pump mechanism". Also, one of the references for the sentence " P. aeruginosa is of great medical importance due to its exhibition of multidrug resistance and its association with serious illnesses" mention a work performed in the nematode C. elegans . It would be right to include more references related to the clinics. Other aspects of this brief report should need clarification, for instance, what is RG in Table 1? What is the difference between perfect and strict cutoff in Fig1A? Figure 2B also needs clarification, since it is difficult for the reader to make an interpretation and get any conclusion. The author claim in the conclusion that the "findings of this brief report could be useful in understanding the chemotherapeutics against antibiotic resistance strains of Pseudomonas pathogens". However, it is not discussed how actually these data could be used or applied. The author should also mention other similar in silico studies already published to compare his results and give consistency to the methodology employed here. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Antimicrobial resistance evolution I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Blanco P. Peer Review Report For: Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.5256/f1000research.28015.r74062) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/9-903/v1#referee-response-74062 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2020 Khan A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 19 Aug 2020 | for Version 1 Asad U. Khan , Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, India 0 Views copyright © 2020 Khan A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Short communication focuses on antibiotic resistance caused by efflux pump overexpression and the use of cryo electron microscopy for protein protein or protein ligand interaction. It also describes the limitations of x ray crystallography. The author also extends the cryo EM use in interparticle motions of the ribosome in different tRNA bound states, its visualization in various conformations upon the introduction of ribosomal-specific substrates and several bacterial membrane proteins to near atomic resolution. Author successfully explain the utility of structural dynamics in drug designing by identifying important residues through solved structures. However, references are missing from the introduction and targeting efflux pumps to mitigate antibiotic resistance section. May be accepted after minor revision. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? No source data required Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Khan AU. Peer Review Report For: Genome-wide analyses reveal antibiotic resistance genes and mechanisms in pathogenic Pseudomonas bacteria [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2020, 9 :903 ( https://doi.org/10.5256/f1000research.28015.r68814) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/9-903/v1#referee-response-68814 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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