Unique immune and cytotoxic responses to SlpA and TcdB differentiate ST01 strains from other Clostridioides difficile Clade 2 Sequence Types

  1. Adriana Badilla-Lobo
  2. Carlos Quesada-Gomez
  3. Esteban Chaves-Olarte
  4. Cesar Rodriguez

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Abstract

Among the five MLST clades encompassing the known global population of the bacterial pathogen Clostridioides difficile, strains from Clade 2 have been given special attention due to the worldwide spread, disease presentation, and prevalence in hospital settings of ST01 strains. We aimed to compare multiple phenotypic properties of clinical Clade 2 ST01 and non-ST01 strains from ST41, ST47, ST67, ST154, and ST638 to identify factors contributing to the higher virulence and epidemic potential that has been historically attributed to the former group of strains. We did not find significant differences in virulence markers such as spore adherence, motility, biofilm formation, and spore disinfectant resistance. Instead, the tested ST01 strains exhibited distinctive surface layer protein A (SlpA) and toxin B (TcdB) profiles that triggered unique immune and cytotoxic responses. These insights challenge the prevailing notion that all Clade 2 strains are highly virulent and inform Public Health strategies for ST01 strain management.

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  2. Access Microbiology

    Comments to Author

    The manuscript of Badilla-Lobo et al. describes their study on characaterization of Clade 2 C. difficile strains where they could not confirm higher virulence properties. They described the methods applied very appropriately and enough deatais and the standards of communicatins is also high. However, the number of studied strains is not high enough it should be discuussed it breifly.

    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?

    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

  3. Access Microbiology

    Comments to Author

    Authors performed phenotypic comparisons between C. difficile ST01 strains and non-ST01 strains (ST47, ST67, ST154, and ST638) and did not find significance differences in spore adhesion, motility, biofilm formation and spore disinfectant resistance. They found that ST01 stains exhibited distinctive slpA and toxin B (TcdB). Major comments: 1) C diff Vegetative cell adhesion to intestinal cells should be performed, since SlpA is involved in vegetative cell adhesion 2) TcdA and CDT profile should be compared 3) Homology levels of SlpA and toxins among tested strains should be analyzed. 4) The C diff supernatants used Fig 2D should be quantified in terms of toxin levels/

    Please rate the manuscript for methodological rigour

    Good

    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?

    No: Major comments: 1) C diff Vegetative cell adhesion to intestinal cells should be performed, since SlpA is involved in vegetative cell adhesion 2) TcdA and CDT profile should be compared 3) Homology levels of SlpA and toxins among tested strains should be analyzed. 4) The C diff supernatants used Fig 2D should be quantified in terms of toxin levels/

  4. Version published to 10.1099/acmi.0.000994.v1 on Access Microbiology