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A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile

Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI), the leading healthcare-related gastrointestinal infection in the world. An association between AMR and CDI outbreaks is well documented, however, data is limited to a fe...

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Autores principales: Imwattana, Korakrit, Rodríguez, César, Riley, Thomas V., Knight, Daniel R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Microbiology Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743556/
https://www.ncbi.nlm.nih.gov/pubmed/34793295
http://dx.doi.org/10.1099/mgen.0.000696
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author Imwattana, Korakrit
Rodríguez, César
Riley, Thomas V.
Knight, Daniel R.
author_facet Imwattana, Korakrit
Rodríguez, César
Riley, Thomas V.
Knight, Daniel R.
author_sort Imwattana, Korakrit
collection PubMed
description Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI), the leading healthcare-related gastrointestinal infection in the world. An association between AMR and CDI outbreaks is well documented, however, data is limited to a few ‘epidemic’ strains in specific geographical regions. Here, through detailed analysis of 10 330 publicly-available C. difficile genomes from strains isolated worldwide (spanning 270 multilocus sequence types (STs) across all known evolutionary clades), this study provides the first species-wide snapshot of AMR genomic epidemiology in C. difficile . Of the 10 330 C . difficile genomes, 4532 (43.9 %) in 89 STs across clades 1–5 carried at least one genotypic AMR determinant, with 901 genomes (8.7 %) carrying AMR determinants for three or more antimicrobial classes (multidrug-resistant, MDR). No AMR genotype was identified in any strains belonging to the cryptic clades. C. difficile from Australia/New Zealand had the lowest AMR prevalence compared to strains from Asia, Europe and North America (P<0.0001). Based on the phylogenetic clade, AMR prevalence was higher in clades 2 (84.3 %), 4 (81.5 %) and 5 (64.8 %) compared to other clades (collectively 26.9 %) (P<0.0001). MDR prevalence was highest in clade 4 (61.6 %) which was over three times higher than in clade 2, the clade with the second-highest MDR prevalence (18.3 %). There was a strong association between specific AMR determinants and three major epidemic C. difficile STs: ST1 (clade 2) with fluoroquinolone resistance (mainly T82I substitution in GyrA) (P<0.0001), ST11 (clade 5) with tetracycline resistance (various tet-family genes) (P<0.0001) and ST37 (clade 4) with macrolide-lincosamide-streptogramin B (MLS(B)) resistance (mainly ermB) (P<0.0001) and MDR (P<0.0001). A novel and previously overlooked tetM-positive transposon designated Tn6944 was identified, predominantly among clade 2 strains. This study provides a comprehensive review of AMR in the global C. difficile population which may aid in the early detection of drug-resistant C. difficile strains, and prevention of their dissemination worldwide.
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spelling pubmed-87435562022-01-10 A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile Imwattana, Korakrit Rodríguez, César Riley, Thomas V. Knight, Daniel R. Microb Genom Research Articles Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI), the leading healthcare-related gastrointestinal infection in the world. An association between AMR and CDI outbreaks is well documented, however, data is limited to a few ‘epidemic’ strains in specific geographical regions. Here, through detailed analysis of 10 330 publicly-available C. difficile genomes from strains isolated worldwide (spanning 270 multilocus sequence types (STs) across all known evolutionary clades), this study provides the first species-wide snapshot of AMR genomic epidemiology in C. difficile . Of the 10 330 C . difficile genomes, 4532 (43.9 %) in 89 STs across clades 1–5 carried at least one genotypic AMR determinant, with 901 genomes (8.7 %) carrying AMR determinants for three or more antimicrobial classes (multidrug-resistant, MDR). No AMR genotype was identified in any strains belonging to the cryptic clades. C. difficile from Australia/New Zealand had the lowest AMR prevalence compared to strains from Asia, Europe and North America (P<0.0001). Based on the phylogenetic clade, AMR prevalence was higher in clades 2 (84.3 %), 4 (81.5 %) and 5 (64.8 %) compared to other clades (collectively 26.9 %) (P<0.0001). MDR prevalence was highest in clade 4 (61.6 %) which was over three times higher than in clade 2, the clade with the second-highest MDR prevalence (18.3 %). There was a strong association between specific AMR determinants and three major epidemic C. difficile STs: ST1 (clade 2) with fluoroquinolone resistance (mainly T82I substitution in GyrA) (P<0.0001), ST11 (clade 5) with tetracycline resistance (various tet-family genes) (P<0.0001) and ST37 (clade 4) with macrolide-lincosamide-streptogramin B (MLS(B)) resistance (mainly ermB) (P<0.0001) and MDR (P<0.0001). A novel and previously overlooked tetM-positive transposon designated Tn6944 was identified, predominantly among clade 2 strains. This study provides a comprehensive review of AMR in the global C. difficile population which may aid in the early detection of drug-resistant C. difficile strains, and prevention of their dissemination worldwide. Microbiology Society 2021-11-18 /pmc/articles/PMC8743556/ /pubmed/34793295 http://dx.doi.org/10.1099/mgen.0.000696 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License.
spellingShingle Research Articles
Imwattana, Korakrit
Rodríguez, César
Riley, Thomas V.
Knight, Daniel R.
A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile
title A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile
title_full A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile
title_fullStr A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile
title_full_unstemmed A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile
title_short A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile
title_sort species-wide genetic atlas of antimicrobial resistance in clostridioides difficile
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743556/
https://www.ncbi.nlm.nih.gov/pubmed/34793295
http://dx.doi.org/10.1099/mgen.0.000696
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