Prioritization of Critical Factors for Surveillance of the Dissemination of Antibiotic Resistance in Pseudomonas aeruginosa: A Systematic Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In their review manuscript “Dissemination of Antibiotic Resistance Genes via Mobile Genetic Elements in Pseudomonas aeruginosa: Prioritizing Critical Factors” the authors provide a broad overview of antibiotic resistance genes (ARG) encompassed on mobile genetic elements (MGE) in Pseudomonas aeruginosa, an important opportunistic pathogen causing life-threatening nosocomial infections. Their comprehensive approach using dual strategy of systematic literature analysis and a genome database survey affords deeper insights into diversity, co-occurrence and distribution of MGEs involved in ARG spreading within the species than literature survey alone would provide. This enabled identification of a number of critical factors (ARGs, associated MGE, and sequence types of the stains that harbour them) that can be of high clinical relevance for the spread of resistance in P. aeruginosa. These factors are discussed in the context of One Health, taking into account the ubiquitous nature of P. aeruginosa, its presence in animals and in the environment, which can be a reservoir of resistance determinants that can spread to human pathogenic strains as well.

The manuscript is appropriately structured and written and is of interest to the wider scientific community.

Comments on the Quality of English Language

The manuscript is well-written and requires only minor adjustments (i.e. some singular/plural checking) particularly in the Abstract. 

Author Response

October 12, 2023

 

Dear Reviewer 2, International Journal of Molecular Sciences (IJMS):

 

I appreciate the comments that you have made regarding our manuscript (Manuscript ID: ijms-2644526). I have carefully read your comments and the manuscript has been rewritten in response to these comments as detailed below.

The amended parts were represented and highlighted in yellow color in the revised manuscript (ijms-2644526-R1.docx).

 

I. Responses to comments of Reviewer 2

 

1. Comment: The manuscript is well-written and requires only minor adjustments (i.e. some singular/plural checking) particularly in the Abstract.

Response: Several grammatical errors were corrected in the revised manuscript.

 

 

I appreciate you for the time in reviewing this submission.

 

With best wishes,

 

 

Prof. Sang Hee Lee

_______________________________________________

National Leading Research Laboratory of Drug Resistance Proteomics

Department of Biological Sciences

Myongji University

116 Myongjiro, Yongin

Gyeonggido, 17058, Republic of Korea

TEL: +82-31-330-6195

FAX: +82-31-335-8249

e-mail: sangheelee@mju.ac.kr

Reviewer 2 Report

Comments and Suggestions for Authors

Title of reviewed article:

Prioritization of critical factors for surveillance of the dissemination of antibiotic resistance in Pseudomonas aeruginosa

Comments

Alignment of aim and findings of the study

The authors investigate the critical factors involved in the dissemination of antibiotic-resistant genes. The authors aim to assess the inventory of mobile ARGs, MGEs and STs in P. aeruginosa. They set out to identify prevalence of these ARGs among the One Health sectors and STs to identify the critical sectors (factors) and STs contributing to the dissemination of ARGs in P. aeruginosa. In the findings, the authors identified 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species and described these as the critical factors set out in this study. Thus, the aim and the findings are aligned.

Relevance of the title:

The title adequately describes the content of the paper. It is submitted in the review section so it should be self-explanatory as a review. But because the authors applied an additional genome database survey with a systematic review, it would be more informative if the title included some information for readers that the data generated from this study is from a combined systematic review and a genome database survey.

Abstract:

There are different preferences as to how to format abstracts. For an article of mixed method study that combines systematic review with a database survey, the authors can clarify by adding “Background”, “Method and Material” and “Findings” or “Results” before each of the subsections in the abstract.

Introduction:

The introduction is clear and well-written.

Method and material:

The first paragraph of the “3. Genome database survey” subsection 3.2 first paragraph, authors introduced intrinsic and acquired resistance as their framework for ARG selection. Since this choice of framework is important for this study and relevant in identifying extrinsic ARG, it is suggested that this part be integrated or moved to the introduction. In particular in the bracket “…(in this study, we excluded mutational resistance but encompassed horizontally acquired resistance)…” and “These acquired ARGs can significantly influence the outcomes of infections following exposure to identical chemical regimens [15]…”. For example, in the last paragraph of the introduction, authors introduced One Health approach in third to last sentence. If the database survey also include extrinsic and intrinsic ARG identification, the approach can be introduced here.

 

Method and material, and findings:

The authors presented rich data.

However, method, material and findings are combined in the manuscript. For instance, section 2. “Systematic literature analysis” which includes 2.1 “Method for systematic literature analysis”, followed by 2.2 MGE linked to ARGs and 2.3 “STs in ARG dissemination…” and 2.4 “Mobile ARGs”. If 2.2 to 2.4 are mix of methods and findings, it will be clearer if the authors can separate and re-arrange the writings please.

The same applies to section 3. “Genome database survey” which includes 3.1 “Method for a genome database survey” which reads as a Methodology section. However, section 3 also includes subsection 3.2 “Intrinsic and acquired ARGs in P. aeruginosa”, 3.3 “Acquired ARGs in One Health sectors” and 3.4 “ARG repertoires and the correlation with One-health sector, ST, and MGEs” which reads as findings. Please separate and clarify.

Method and material

It will be helpful for authors to succinctly describe in either a separate or existing Method and Material section the information or methods that are described in the subtitle of the Figures and heat map. Authors can help clarify the Methods they use to integrate the Systematic Review and Genome data survey that can be unique in their approach and is not described clearly in the current writing. For example, authors can describe their approach “…clustering and distinct clades were obtained by the Bray-Curtis dissimilarity matrix of ARG repertoires of all genomes belonging to each ST coded with ARG names. In addition, these names are identified for their coincidence of the prevalent ARGs in both systematic literature analysis and genome database survey”.

In addition, there are statistical tests conducted in this study with findings described on Page 7 line 255, Page 10 line 361 and Page 11 line 397. Though correlation and Pearson correlation (Page 9 line 358) are implicated or described, it is a common practice to state type of statistical test authors conducted in the Method section.

Discussion

The authors discussed the strength of including genome database survey in future studies. There is less discussion of the findings from the data identified in this study. For instance, in the number of detected ARGs and number of kind of ARGs against antibiotics such as aminoglycosides, beta-lactams, phenicol and quinolone. Can authors add discussion on these findings? And how these compare to the prevalence identified in the literature reviewed? In terms of One Health and based on the findings in this study, can the author discuss ARGs based on systematic review and genome database survey, that are abundant in the environment, animals, humans and in what settings the systematic review can inform readers such as human hospitals, communities, water or soil, or other settings?  

Style and fonts

There are yellow highlights throughout the manuscript. Please undo in final submission.

 

Author Response

Please see the attachment.

Author Response File: Author Response.docx