Drug-Driven Phenotypic Convergence Supports Rational Treatment Strategies of Chronic Infections.

ABSTRACT: Chronic Pseudomonas aeruginosa infections evade antibiotic therapy and are associated with mortality in cystic fibrosis (CF) patients. We find that in vitro resistance evolution of P. aeruginosa toward clinically relevant antibiotics leads to phenotypic convergence toward distinct states. These states are associated with collateral sensitivity toward several antibiotic classes and encoded by mutations in antibiotic resistance genes, including transcriptional regulator nfxB. Longitudinal analysis of isolates from CF patients reveals similar and defined phenotypic states, which are associated with extinction of specific sub-lineages in patients. In-depth investigation of chronic P. aeruginosa populations in a CF patient during antibiotic therapy revealed dramatic genotypic and phenotypic con

SUBMITTER: Imamovic L 

PROVIDER: S-EPMC5766827 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature