Gain-of-Function Mutations in Acid Stress Response (evgS) Protect Escherichia coli from Killing by Gallium Nitrate, an Antimicrobial Candidate.

ABSTRACT: Widespread antimicrobial resistance encourages repurposing/refining of nonantimicrobial drugs for antimicrobial indications. Gallium nitrate (GaNt), an FDA-approved medication for cancer-related hypercalcemia, recently showed good activity against several clinically significant bacteria. However, the mechanism of GaNt antibacterial action is still poorly understood. In the present work, resistant and tolerant mutants of Escherichia coli were sought via multiple rounds of killing by GaNt. Multiround-enrichment yielded no resistant mutant; whole-genome sequencing of one representative GaNt-tolerant mutant uncovered mutations in three genes (evgS, arpA, and kdpD) potentially linked to protection from GaNt-mediated killing. Subsequent genetic analysis ruled out a ro

SUBMITTER: Zeng J 

PROVIDER: S-EPMC8092542 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature