Localized pmrB hypermutation drives the evolution of colistin heteroresistance.

ABSTRACT: Colistin has emerged as an important last line of defense for the treatment of infections caused by antibiotic-resistant gram-negative pathogens, but colistin resistance remains poorly understood. Here, we investigate the responses of ≈1,000 populations of a multi-drug-resistant (MDR) strain of P. aeruginosa to a high dose of colistin. Colistin exposure causes rapid cell death, but some populations eventually recover due to the growth of sub-populations of heteroresistant cells. Heteroresistance is unstable, and resistance is rapidly lost under culture in colistin-free medium. The evolution of heteroresistance is primarily driven by selection for heteroresistance at two hotspot sites in the PmrAB regulatory system. Localized hypermutation of pmrB generates colistin resistance at 10^3</

SUBMITTER: Kapel N 

PROVIDER: S-EPMC9189680 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature