Emergence of a plasmid-borne multidrug resistance gene cfr(C) in foodborne pathogen Campylobacter

Abstract

Objectives: To identify and characterize a novel cfr variant that recently emerged and confers multidrug resistance in Campylobacter, a major foodborne pathogen. Methods: WGS was initially used to identify the cfr(C) gene in Campylobacter isolates and its function was further verified by cloning into an antibiotic-susceptible Campylobacter jejuni strain. Distribution of cfr(C) in various Campylobacter isolateswas determined by PCR analysis. Genotyping of cfr(C)-positive strains was done by PFGE and MLST. Results: The cfr(C) gene is predicted to encode a protein that shares 55.1% and 54.9% identity with Cfr and Cfr(B), respectively. cfr(C) was located on a conjugative plasmid of ~48 kb. Cloning of cfr(C) into C. jejuni NCTC 11168 and conjugative transfer of the cfr(C)-containing plasmid confirmed its role in conferring resistance to phenicols, lincosamides, pleuromutilins and oxazolidinones, and resulted in an 8-256-fold increase in their MICs in both C. jejuni and Campylobacter coli. The cfr(C) gene was detected in multiple C. coli (34 of 344; 10%) isolates derived from different cattle farms in different states, and molecular typing of the cfr(C)-positive C. coli isolates revealed its spread mainly via clonal expansion. Conclusions: These results identify cfr(C) as a new multidrug resistance mechanism in Campylobacter and suggest the potential transmission of this mechanism via the foodborne route, warranting enhanced efforts to monitor its spread in Campylobacter and other foodborne pathogens.