Immunosuppression broadens evolutionary pathways to drug resistance and treatment failure during Acinetobacter baumannii pneumonia in mice.

ABSTRACT: Acinetobacter baumannii is increasingly refractory to antibiotic treatment in healthcare settings. As is true of most human pathogens, the genetic path to antimicrobial resistance (AMR) and the role that the immune system plays in modulating AMR during disease are poorly understood. Here we reproduced several routes to fluoroquinolone resistance, performing evolution experiments using sequential lung infections in mice that are replete with or depleted of neutrophils, providing two key insights into the evolution of drug resistance. First, neutropenic hosts acted as reservoirs for the accumulation of drug resistance during drug treatment. Selection for variants with altered drug sensitivity profiles arose readily in the absence of neutrophils, while immunocompetent animals restricted the a

SUBMITTER: Huo W 

PROVIDER: S-EPMC9159950 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature