Analysis of AcrB in Klebsiella pneumoniae reveals natural variants promoting enhanced multidrug resistance.

ABSTRACT: Infections caused by Klebsiella pneumoniae are often difficult to manage due to the high frequency of multidrug resistance, often conferred by efflux pumps. In this study, we analyzed sequence variations of the major RND family multidrug efflux pump AcrB from 387 assembled K. pneumoniae genomes. We confirm that AcrB is a highly-conserved efflux pump in K. pneumoniae, and identified several variants that were prevalent in clinical isolates. Molecular dynamics analyses on two of these variants (L118M and S966A) suggested conformational changes that may correlate with increased drug efflux capabilities. The L118M change resulted in enhanced protein rigidity while the flexibility of drug binding pockets was stable or increased, and the interactions between the proximal pockets and water molecu

SUBMITTER: Li Y 

PROVIDER: S-EPMC9035133 | biostudies-literature | 2022 Mar-Apr

REPOSITORIES: biostudies-literature