Abstract
The increasing incidence of primary and recurring Clostridioides difficile infections (CDI), which evade current treatment strategies, reflects the changing biology of C difficile. Here, we describe a putative plasmid-mediated mechanism potentially driving decreased sensitivity of C difficile to vancomycin treatment. We identified a broad host range transferable plasmid in a C difficile strain associated with lack of adequate response to vancomycin treatment. The transfer of this plasmid to a vancomycin-susceptible C difficile isolate decreased its susceptibility to vancomycin in vitro and resulted in more severe disease in a humanized mouse model. Our findings suggest plasmid acquisition in the gastrointestinal tract to be a possible mechanism underlying vancomycin treatment failure in patients with CDI, but further work is needed to characterize the mechanism by which plasmid genes determine vancomycin susceptibility in C difficile.
Original language | English (US) |
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Pages (from-to) | 941-945.e8 |
Journal | Gastroenterology |
Volume | 160 |
Issue number | 3 |
DOIs | |
State | Published - Feb 2021 |
Keywords
- Amidase
- Antimicrobial Resistance
- Cell Wall Peptidoglycan
- Gram Positive
ASJC Scopus subject areas
- Hepatology
- Gastroenterology