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

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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 10330 publiclyavailable 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 10330 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 (MLSB) 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.
Original languageEnglish
Article number000696
JournalMicrobial Genomics
Issue number11
Publication statusPublished - 18 Nov 2021


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