Characterization of IncHI1B Plasmids Encoding Efflux Pump in Carbapenem-Resistant , , and Strains.

Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, , and its variants, and , encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three -harboring species strains, collected from two teaching tertiary hospitals in China, including one , one , and one . The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that and strains were resistant to tigecycline with MIC values of 4μg/ml, whereas the was susceptible to tigecycline with an MIC value of 1μg/ml. The clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-β-lactamase gene . Conjugation experiments showed that all three plasmids were capable of self-transfer conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism has spread into different species, and clinical susceptibility testing may fail to detect. The co-occurrence of and in the same plasmid is of particular public health concern as the convergence of "mosaic" plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of encoding resistance should be considered.