Plasmid Acquisition Alters Vancomycin Susceptibility in Clostridioides difficile

Meng Pu, Janice M. Cho, Scott A. Cunningham, Gaurav K. Behera, Sarah Becker, Talal Amjad, Kerryl E. Greenwood-Quaintance, Helena Mendes-Soares, Yava Jones-Hall, Patricio R. Jeraldo, Jun Chen, Gary Dunny, Robin Patel, Purna C. Kashyap

Research output: Contribution to journalShort surveypeer-review

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 languageEnglish (US)
Pages (from-to)941-945.e8
JournalGastroenterology
Volume160
Issue number3
DOIs
StatePublished - Feb 2021

Keywords

  • Amidase
  • Antimicrobial Resistance
  • Cell Wall Peptidoglycan
  • Gram Positive

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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