Discovering interrelated natural mutations of efflux pump KmrA from Klebsiella pneumoniae that confer increased multidrug resistance.

ABSTRACT: Klebsiella pneumoniae is a notorious pathogen that can cause multiorgan infections, which is difficult to treat mainly due to the widely distributed efflux pumps. Our previous research discovered the upregulation of efflux pump KmrA conferred enhanced antibiotic resistance, while the export mechanism and its natural mutations across K. pneumoniae isolates remain unclear. Herein, we analyzed the natural mutations of KmrA across 830 K. pneumoniae genomes to discover interrelated amino-acid substitutions (simultaneously occurred substitutions) that increase drug export. We identified two variants that contain triple amino-acid substitutions near the periplasmic side and then confirmed their roles in enhancing multidrug resistance of recombinant K. pneumoniae strains. Molecular dynamics simula

SUBMITTER: Li Y 

PROVIDER: S-EPMC9083138 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature