Reversion of a RND transporter pseudogene reveals latent stress resistance potential in Brucella ovis.

ABSTRACT: Small-molecule screens can advance therapeutic discovery and uncover new features of pathogen biology. Through a luminescence-based screen, we identified clinically approved dihydropyridines that impaired fitness of the intracellular pathogen Brucella ovis in mammalian phagocytes. Given that dihydropyridines block mammalian L-type calcium channels, and based on our observation that drug treatment perturbed calcium and manganese levels in host phagocytes, we initially hypothesized a host-directed mechanism of action. However, dose-response assays in axenic medium showed that dihydropyridines have direct antimicrobial effects. To explore the genetic basis of dihydropyridine sensitivity, we selected for B. ovis mutants capable of growing in the presence of cilnidipine, a representative compou

SUBMITTER: Kim T 

PROVIDER: S-EPMC12306736 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature