Targeting a bacterial stress response to enhance antibiotic action.

ABSTRACT: This report describes the identification and analysis of a 2-component regulator of Pseudomonas aeruginosa that is a potential aminoglycoside antibiotic combination therapy target. The regulator, AmgRS, was identified in a screen of a comprehensive, defined transposon mutant library for functions whose inactivation increased tobramycin sensitivity. AmgRS mutations enhanced aminoglycoside action against bacteria grown planktonically and in antibiotic tolerant biofilms, against genetically resistant clinical isolates, and in lethal infections of mice. Drugs targeting AmgRS would thus be expected to enhance the clinical efficacy of aminoglycosides. Unexpectedly, the loss of AmgRS reduced virulence in the absence of antibiotics, indicating that its inactivation could protect against infection

SUBMITTER: Lee S 

PROVIDER: S-EPMC2732827 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature