Plasmid-mediated dissemination of blaKPC-3 and multidrug resistance genes among different species of Klebsiella.

Carbapenem resistance is a serious threat to public health because carbapenems are used as last-resort antibiotics. Carbapenem resistance gene KPC (Klebsiella pneumoniae carbapenemase) inactivates a broad range of β-lactam substrates. In this manuscript, we examined intra-host transmission of blaKPC-3 via interspecies gene transfer. Two carbapenem-resistant Klebsiella pneumoniae isolates and one Klebsiella michiganensis isolate were identified from two patients. Genetic relations of these isolates were investigated with whole-genome sequencing (WGS). Hybrid assembly of bacterial genomes showed the three isolates carried plasmids that harbor common antimicrobial resistance (AMR) gene clusters that confer multidrug-class resistance, including carbapenems. Our results suggest that AMR gene clusters are disseminated across the species as fragments rather than as complete, intact plasmids.IMPORTANCEAn antimicrobial resistance gene cluster encompassing multiple drug classes on plasmids could lead a drug-susceptible pathogen to gain multidrug resistance. Interspecies gene transfer enables K. michiganensis to become multidrug-resistant through the acquisition of clustered, plasmid-encoded resistance genes spanning multiple antibiotic classes.