Comparative Genomics Analysis of six Cutibacterium acnes Strains Isolated from Contaminated Platelet Concentrates

  1. Annika Flint
  2. Dilini Kumaran
  3. Kelly Weedmark
  4. Franco Pagotto
  5. Sandra Ramirez-Arcos

Reviewed by

Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

Cutibacterium acnes is a bacterial skin commensal that is often isolated during routine testing of blood products like platelet concentrates (PCs). Due to the slow growing nature of this bacterium in culture media, C. acnes contaminated PCs are often transfused into vulnerable patients before retrieval of these units can be initiated. This study aimed at obtaining the whole genome sequence of six C. acnes isolates derived from contaminated PCs and to phylotype, compare, and assess their genetic backgrounds. Furthermore, the whole genomes of the PC isolates were compared to clinical isolates obtained from different sites and types of infection. The results indicate that these PC isolates assessed belong to four phylotypes namely: IA, IB, II and III. Whole genome comparisons identified differences in the virulence profiles of the isolates and provides a foundation for future studies aimed at evaluating the risk to transfusion patients by determining whether the expression of virulence factors is impacted in the PC storage environment.

Article activity feed

  2. Version published to 10.1099/acmi.0.000938.v2 on Access Microbiology
  3. Access Microbiology

    The work presented is clear and the arguments well formed. This study would be a valuable contribution to the existing literature. This is a study that would be of interest to the field and community. The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments.

  4. Access Microbiology

    Comments to Author

    This study provides valuable insights into the genetic diversity and potential pathogenicity of C. acnes strains found in contaminated platelet concentrates. My primary concern lies with the methodology employed to analyze the antimicrobial resistance determinants. Specifically, I believe that reducing the minimum proportion of identical amino acids for establishing homology to known resistance genes may lead to inaccurate inferences. A 0.3 threshold is excessively low for most applications and could generate false positives. This concern is compounded by the absence of Minimum Inhibitory Concentration (MIC) data for the isolates. I mean, if this approach would be backed with the data of your study, for example if BPNBT-19195 and BPNBT-19329 had significantly lower MICs for Trimetropin, this could appear more reasonable. Therefore, and taking into account that comprehensive genomic analyses of C. acnes, particularly with respect to antimicrobial resistance, are still relatively limited, correlating the identified resistance genes with actual phenotypic resistance profiles through MIC testing would significantly strengthen the study's conclusions and contribute valuable data to the field. In particular, Table 2 would benefit from greater clarity, explicitly stating the percentage of identity to the reference sequence for each putative resistance gene would enhance the transparency and interpretability of the results. Minor typos: line 136 "(-c 0.9 and -p 0.3)" at least in the latest versions of amrfinder -p is an argument for the protein files and I assume you used -i instead. line 178 C. acnes not italicized

    Please rate the manuscript for methodological rigour

    Satisfactory

    Please rate the quality of the presentation and structure of the manuscript

    Good

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  5. Access Microbiology

    Comments to Author

    - Although the isolation of Cutibacterium acnes was carried out as part of a routine examination of blood products, the methodology of the study should include a declaration of ethical clearance. - Line 35: the sentence "This study aimed at obtaining the whole genome sequence...", is better to be replaced with "This study aimed to obtain the whole genome sequence..." - Line 40: remove the word "enhanced" from the sentence "Potential enhanced risk". - Line 46: replace the word "those" in the sentence "with most of those" with "these". - Line 49: add the word "the" before the word "growth" to this sentence "...restricts growth of anaerobic bacteria such as C. acnes." - Lines 58-78: in the introduction, the potential clinical relevance of C. acnes contamination in platelet concentrates was highlighted, better to explore some clinical outcomes of such contaminations a little bit in depth. - Line 75: replace the word "even" in the sentence "...and has even been linked to prostate cancer." with "also" to be "has also been associated with prostate cancer.". - Line 175: The discussion highlights results such as phylotyping and genome-wide comparisons but does not include rigorous statistical analysis to confirm their validity., so better to show some statistical analysis. - General recommendation: the overall language and grammar throughout the manuscript need a little bit revision.

    Please rate the manuscript for methodological rigour

    Very good

    Please rate the quality of the presentation and structure of the manuscript

    Very good

    To what extent are the conclusions supported by the data?

    Strongly support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  6. Access Microbiology

    Comments to Author

    Comparative Genomics Analysis of six Cutibacterium acnes Strains Isolated from Contaminated Platelet Concentrates The study focuses on the genomic analysis of six Cutibacterium acnes strains isolated from contaminated platelet concentrates (PCs). The authors aim to determine the genetic diversity and potential virulence profiles of these strains, especially concerning their phylotypes and associated virulence factors. They draw comparisons between these PC isolates and clinical strains associated with infections, highlighting the potential risk of C. acnes in transfusion settings. Here are some important areas which need improvement 1. Some sections, especially methods and results, are dense and could benefit from more concise language. Simplifying complex descriptions while aiming at convey a specific points per sentence would improve readability. 2. Including a description of the routine method for screening PCs for bacterial contamination would give readers a clear understanding of current limitations. i. For instance, mentioning commonly used culture techniques, their timing, and their limitations (like the fact that C. acnes grows slowly in aerobic conditions) would help explain why contamination by this particular bacteria might be easily missed. ii. Additionally, it's worth considering that some strains of C. acnes may have gone undetected in this study, potentially including those responsible for infections in patients. 3. It could be helpful to discuss briefly if other bacteria were detected in the studied PCs and if they had similar genomic characteristics regarding virulence and antimicrobial resistance. Such comparisons could underscore the unique nature of C. acnes and its potential pathogenicity in transfusion settings. 4. Although the authors discuss the phylotypes of the isolates, additional context or clarification on the clinical relevance of each phylotype (IA, IB, II, III) would strengthen the argument about their infection potential. 5. While the study identifies four C. acnes phylotypes in PCs, further analysis on why phylotypes IA, IB, and II are associated with infection while phylotype III is not would be beneficial. Adding a deeper discussion on genetic or functional differences that might explain these patterns could enrich the paper's relevance to clinical outcomes. 6. While the study addresses potential clinical risks, expanding on the implications for transfusion medicine and considering additional clinical data would enhance the applicability. 7. While the identification of virulence and AMR determinants is thorough, it may be beneficial to explicitly discuss how these genes might interact with the unique environment of PCs, or how they might modulate infection risk in transfusion settings. 8. The study suggests that the PC environment might alter C. acnes virulence factor expression. Including experimental data or references on how similar anaerobic pathogens respond to the PC environment could provide more context to this hypothesis. 9. Apart from the antimicrobial resistance genes having potential adaptive advantages, but it would be beneficial please highlight on: 10. Any known clinical impacts of these resistances in chronic or post-transfusion infections, as there's mention of resistance factors but limited context on their clinical relevance. 11. Whether these resistance genes could persist post-transfusion and how they might impact treatment options in cases of infection. 12. Since the study provides significant evidence of pathogenic potential within PCs, it might be valuable to briefly discuss any recommendations or precautions that could be taken to minimize contamination risks. If no formal recommendations are proposed, mention ongoing research or future directions. 13. Furthermore recommending specific follow-up studies investigating the role of the PC storage environment in modulating virulence gene expression or exploring methods to rapidly detect C. acnes contamination before transfusion could be valuable next steps. 14. Additionally, some areas could benefit from better organization, particularly around complex concepts, to prevent information overload for readers. Ensuring consistent formatting of references and defining specialized terms or abbreviations on first use could also support a multidisciplinary audience in fully engaging with the research findings. 15. The limitations of using in silico methods for virulence factor predictions should be acknowledged. Additionally, highlighting potential limitations in genomic analyses, such as the inability to capture expression differences under different conditions, would provide a balanced view. 16. Figures depicting phylogenetic trees and genome alignments (e.g., Figures 1 and 2) would benefit from increased resolution or annotation to improve clarity for readers. 17. Consider Alternative Formatting for Tables: Tables 2 and 3, which list resistance and virulence genes, are extensive and could be supplemented with visual aids or focused discussion on the most clinically relevant genes.

    Please rate the manuscript for methodological rigour

    Good

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Strongly support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  7. Version published to 10.1099/acmi.0.000938.v1 on Access Microbiology