Plasmid Acquisition Alters Vancomycin Susceptibility in Clostridioides difficile.
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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 invitro 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.
author list (cited authors)
Pu, M., Cho, J. M., Cunningham, S. A., Behera, G. K., Becker, S., Amjad, T., ... Kashyap, P. C.
complete list of authors
Pu, Meng||Cho, Janice M||Cunningham, Scott A||Behera, Gaurav K||Becker, Sarah||Amjad, Talal||Greenwood-Quaintance, Kerryl E||Mendes-Soares, Helena||Jones-Hall, Yava||Jeraldo, Patricio R||Chen, Jun||Dunny, Gary||Patel, Robin||Kashyap, Purna C