(p)ppGpp-mediated GTP homeostasis ensures survival and antibiotic tolerance of Staphylococcus aureus.

ABSTRACT: Antibiotic tolerance in non-growing bacterial populations is of major concern regarding antibiotic treatment failures. Whether and how the messenger molecule (p)ppGpp contributes to this phenomenon is controversial. We show for Staphylococcus aureus that (p)ppGpp-dependent restriction of the GTP pool is essential for the culturability of starved cells. Survival was independent of the GTP-responsive regulator CodY. Elevated GTP levels in a starved (p)ppGpp-deficient mutant led to quiescent state characterised by alterations in membrane architecture and a decrease of the proton motive force (PMF). This was accompanied by dysregulation of components involved in electron transport, including qoxABCD, encoding the main terminal oxidase. Increasing qoxABCD transcription by mutation of the transc

SUBMITTER: Salzer A 

PROVIDER: S-EPMC11953324 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature