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Comparative genomics of Clostridioides difficile toxinotypes identifies module-based toxin gene evolution
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Janezic, Sandra, Dingle, Kate, Alvin, Joseph, Accetto, Tomaž, Didelot, Xavier, Crook, Derrick W., Lacy, D. Borden and Rupnik, Maja (2020) Comparative genomics of Clostridioides difficile toxinotypes identifies module-based toxin gene evolution. Microbial Genomics, 6 (10). doi:10.1099/mgen.0.000449 ISSN 2057-5858.
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Official URL: http://dx.doi.org/10.1099/mgen.0.000449
Abstract
Clostridioides difficile is a common cause of nosocomial diarrhoea. Toxins TcdA and TcdB are considered to be the main virulence factors and are encoded by the PaLoc region, while the binary toxin encoded in the CdtLoc region also contributes to pathogenicity. Variant toxinotypes reflect the genetic diversity of a key toxin-encoding 19 kb genetic element (the PaLoc). Here, we present analysis of a comprehensive collection of all known major C. difficile toxinotypes to address the evolutionary relationships of the toxin gene variants, the mechanisms underlying the origin and development of variability in toxin genes and the PaLoc, and the relationship between structure and function in TcdB variants. The structure of both toxin genes is modular, composed of interspersed blocks of sequences corresponding to functional domains and having different evolutionary histories, as shown by the distribution of mutations along the toxin genes and by incongruences of domain phylogenies compared to overall C. difficile cluster organization. In TcdB protein, four mutation patterns could be differentiated, which correlated very well with the type of TcdB cytopathic effect (CPE) on cultured cells. Mapping these mutations to the three-dimensional structure of the TcdB showed that the majority of the variation occurs in surface residues and that point mutation at residue 449 in alpha helix 16 differentiated strains with different types of CPE. In contrast to the PaLoc, phylogenetic trees of the CdtLoc were more consistent with the core genome phylogenies, but there were clues that CdtLoc can also be exchanged between strains.
Item Type: | Journal Article | ||||||
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Subjects: | Q Science > QR Microbiology | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
Library of Congress Subject Headings (LCSH): | Clostridium difficile, Toxins, Gene mapping, Clostridium difficile -- Research | ||||||
Journal or Publication Title: | Microbial Genomics | ||||||
Publisher: | Microbiology Society | ||||||
ISSN: | 2057-5858 | ||||||
Official Date: | 8 October 2020 | ||||||
Dates: |
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Volume: | 6 | ||||||
Number: | 10 | ||||||
DOI: | 10.1099/mgen.0.000449 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 20 October 2020 | ||||||
Date of first compliant Open Access: | 20 October 2020 | ||||||
RIOXX Funder/Project Grant: |
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