Molecular mechanisms and epidemiology of fosfomycin resistance in enterococci isolated from patients at a teaching hospital in China from 2013 to 2016

Abstract Objectives The aim of this study was to investigate the mechanisms of fosfomycin resistance and epidemiological characteristics in fosfomycin-resistant enterococci. Methods A collection of 761 enterococcal clinical isolates were studied, investigated the susceptibility of fosfomycin using the agar dilution method and analyzed for mechanisms of resistance by polymerase chain reaction and quantitative real-time PCR. Furthermore, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed to analyze the molecular epidemiology of fosfomycin-resistant isolates. Results In this study, 0.3% (1/372) of Enterococcus faecalis and 4.9% (19/389) of Enterococcus faecium were found to be resistant to fosfomycin. Among 20 fosfomycin-resistant strains, five harbored fosB, ten carried multiple amino acid substitutions in MurA and six showed high expression level of fosX gene. Of note, one of these strains carried fosB gene and amino acid mutation in MurA simultaneously. Further, a high degree of homology in the most fosfomycin-resistant enterococci was confirmed using MLST and PFGE. Conclusions Our finding demonstrated that the fosB gene, mutations in the fosfomycin target enzyme MurA, and a high expression level of fosX were the resistance mechanisms in these enterococci.