Molecular characterization of carbapenem-resistant and virulent plasmids in <i>Klebsiella pneumoniae</i> from patients with bloodstream infections in China

Abstract

Bloodstream infections (BSIs) caused by carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) are potentially life-threatening and an urgent threat to public health. The present study aims to clarify the characteristics of carbapenemase-encoding and virulent plasmids, and their interactions with the host bacterium. A total of 425 <i>Kp</i> isolates were collected from the blood of BSI patients from nine Chinese hospitals, between 2005 and 2019. Integrated epidemiological and genomic data showed that ST11 and ST307 <i>Kp</i> isolates were associated with nosocomial outbreak and transmission. Comparative analysis of 147 <i>Kp</i> genomes and 39 completely assembled chromosomes revealed extensive interruption of <i>acrR</i> by IS<i>Kpn26</i> in all <i>Kp</i> carbapenemase-2 (KPC-2)-producing ST11 <i>Kp</i> isolates, leading to activation of the AcrAB-Tolc multidrug efflux pump and a subsequent reduction in susceptibility to the last-resort antibiotic tigecycline and six other antibiotics. We described 29 KPC-2 plasmids showing diverse structures, two virulence plasmids in two KPC-2-producing <i>Kp</i>, and two novel multidrug-resistant (MDR)-virulent plasmids. This study revealed a multifactorial impact of KPC-2 plasmid on <i>Kp</i>, which may be associated with nosocomial dissemination of MDR isolates.