Dear Dr. Verschuuren,

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Gabriel Trueba, PhD

Academic Editor

PLOS ONE

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2. Thank you for stating in your Funding Statement:

[The MODERN studies (Understanding and modelling reservoirs, vehicles and transmission of ESBL-producing Enterobacteriaceae in the community and long term care facilities) were part of a Joint Programming Initiative on Antimicrobial Resistance collaborative  research project, under the 2016 Joint Call framework (Transnational Research Projects on the Transmission Dynamics of Antibacterial Resistance). It received funding from the following national research agencies: Instituto de Salud Carlos III (grant no. AC16/00076), Netherlands Organization for Health Research and Development (grant no. 681055, 547001004), Swiss National Science Foundation (grant no. 40AR40-173608), German Federal Ministry of Education and Research (grant no. 01KI1701), the French Agence Nationale de la Recherche (grant no. ANR-16-JPEC-0007-03), and UK Medical Research Council (grant no. MR/R004536/1). Elena Salamanca, and Jesús Rodríguez-Baño received support for research from by the Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund A way to achieve Europe, Operative Program Intelligence Growth 2014–2020.].

Please provide an amended statement that declares *all* the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.  Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement.

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

4. Thank you for stating the following financial disclosure:

[The MODERN studies (Understanding and modelling reservoirs, vehicles and transmission of ESBL-producing Enterobacteriaceae in the community and long term care facilities) were part of a Joint Programming Initiative on Antimicrobial Resistance collaborative  research project, under the 2016 Joint Call framework (Transnational Research Projects on the Transmission Dynamics of Antibacterial Resistance). It received funding from the following national research agencies: Instituto de Salud Carlos III (grant no. AC16/00076), Netherlands Organization for Health Research and Development (grant no. 681055, 547001004), Swiss National Science Foundation (grant no. 40AR40-173608), German Federal Ministry of Education and Research (grant no. 01KI1701), the French Agence Nationale de la Recherche (grant no. ANR-16-JPEC-0007-03), and UK Medical Research Council (grant no. MR/R004536/1). Elena Salamanca, and Jesús Rodríguez-Baño received support for research from by the Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund A way to achieve Europe, Operative Program Intelligence Growth 2014–2020.].

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

5. Thank you for stating the following in your manuscript:

[The MODERN studies (Understanding and modelling reservoirs, vehicles and transmission of ESBL-producing Enterobacteriaceae in the community and long term care facilities) were part of a Joint Programming Initiative on Antimicrobial Resistance collaborative  research project, under the 2016 Joint Call framework (Transnational Research Projects on the Transmission Dynamics of Antibacterial Resistance). It received funding from the following national research agencies: Instituto de Salud Carlos III (grant no. AC16/00076), Netherlands Organization for Health Research and Development (grant no. 681055, 547001004), Swiss National Science Foundation (grant no. 40AR40-173608), German Federal Ministry of Education and Research (grant no. 01KI1701), the French Agence Nationale de la Recherche (grant no. ANR-16-JPEC-0007-03), and UK Medical Research Council (grant no. MR/R004536/1). Elena Salamanca, and Jesús Rodríguez-Baño received support for research from by the Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund A way to achieve Europe, Operative Program Intelligence Growth 2014–2020.]

We note that you have provided funding information that is currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

[The MODERN studies (Understanding and modelling reservoirs, vehicles and transmission of ESBL-producing Enterobacteriaceae in the community and long term care facilities) were part of a Joint Programming Initiative on Antimicrobial Resistance collaborative  research project, under the 2016 Joint Call framework (Transnational Research Projects on the Transmission Dynamics of Antibacterial Resistance). It received funding from the following national research agencies: Instituto de Salud Carlos III (grant no. AC16/00076), Netherlands Organization for Health Research and Development (grant no. 681055, 547001004), Swiss National Science Foundation (grant no. 40AR40-173608), German Federal Ministry of Education and Research (grant no. 01KI1701), the French Agence Nationale de la Recherche (grant no. ANR-16-JPEC-0007-03), and UK Medical Research Council (grant no. MR/R004536/1). Elena Salamanca, and Jesús Rodríguez-Baño received support for research from by the Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund A way to achieve Europe, Operative Program Intelligence Growth 2014–2020.].

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

6. Please amend the manuscript submission data (via Edit Submission) to include authors TD Verschuuren, J Guther, ME Riccio, D Martak, E Salamanca, S Göpel, N Conzelmann, J Scharringa, P Musicha, IB Autenrieth, BS Cooper, D Hocquet, E Tacconelli, J Rodriguez-Baño, S Harbarth, AC Fluit, S Peter, and JAJW Kluytmans.

7. Please amend your authorship list in your manuscript file to include authors Tess Verschuuren, Julia Guther, Maria Eugenia Riccio, Daniel Martak, Elena Salamanca, Siri Göpel, Nadine Conzelmann, Jelle Scharringa, Patrick Musicha, Ingo B. Autenrieth, Ben S. Cooper, Didier Hocquet, Evelina Tacconelli, Jesus Rodriguez-Baño, Stephan Harbarth, Ad C. Fluit, Silke Peter, and Jan A.J.W. Kluytmans.

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If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

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[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: The authors present a study on the epidemiology of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae. The work is based on isolates collected from five European metropolitan areas, which were genome-sequenced and analyzed using in silico approaches. Analyses of antimicrobial resistance gene (ARG) content, core genome multilocus sequence typing (cgMLST), and core genome comparisons allowed the authors to explore clonal relationships between isolates. The topic is of public health relevance, and the manuscript is generally well-written and easy to follow.

Minor comments:

The possible role of the hospital or LTCF environment as a reservoir or amplifier of multidrug-resistant bacteria is not discussed. This would be particularly relevant given the healthcare-associated nature of the study population.

The limitations section occupies more than half of the discussion and could be slightly condensed to improve balance with the rest of the text.

While the authors mention the need for long-read sequencing, they could elaborate more specifically on the types of questions that such technology would enable (e.g., plasmid structure, transmission dynamics of mobile genetic elements).

Would the authors consider routine genomic surveillance in hospitals or LTCFs useful? This could be suggested as a potential recommendation for future practice.

Reviewer #2: The study addresses a very important and pertinent issue. Epidemiological, laboratory and statistical methodology was great and innovative. As far as results are concerned, there was a bit if discrepancy between the text on line 158 and the table where text says Table 1 shows mrc-1 gene in an ESBL-EC strain while text indicates it is in an ESBL- Kp!!! Otherwise the results are well represented and easy to understand. The discussion analyses the results notes the limitations. Overall study is well designed, done and excellently written.

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: Yes:  Henry Mawerere Kajumbula

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Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae from human carriage, the human-polluted environment, and food: molecular epidemiology of two prospective cohorts in five European metropolitan areas

PONE-D-25-20088R1

Dear Dr. Verschuuren,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Gabriel Trueba, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Reviewer #1: (No Response)

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: No

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