Convergent evolution of antibiotic resistance mechanisms between pyrrolobenzodiazepines and albicidin in multidrug resistant Klebsiella pneumoniae.

ABSTRACT: Pyrrolobenzodiazepines (PBDs) containing C8-linked aliphatic heterocycles have been developed as a new class of potent antibacterial compounds. They are active against multidrug resistant Gram-negative pathogens, including Klebsiella pneumoniae. When isolates were exposed to PBDs, they acquired resistance, with significant increases in inhibitory concentrations. Resistant strains showed mutations in genes associated with resistance to albicidin, specifically tsx and merR-family regulator albA. Heterologous expression of AlbA in E. coli and introducing the L120Q AlbA resistance-mediating modification into the genome of a sensitive K. pneumoniae strain conferred PBD and albicidin resistance. Proteomic analysis of the resistant strains showed elevated AlbA protein levels compared to isogenic

SUBMITTER: Surani YM 

PROVIDER: S-EPMC12144233 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature