Relapsing bacterial infections require prolonged and repetitive antibiotic treatment schedules associated with the emergence of antibiotic resistance. Small reservoirs of bacteria called persisters underlie relapsing infections. Persisters are genetically antibiotic-sensitive bacterial cells that transiently enter a non-proliferative state marked by low drug susceptibility. Persisters often reside in macrophages where they are protected from drug-mediated killing.

Using invasive non-typhoidal Salmonella as a model, we aim to identify host-targeted perturbations that can disrupt the persister-permissive macrophage niche and promote persister eradication without inducing immunopathology. If successful, this will pave the way for development of next-generation immunomodulatory therapies to treat relapsing bacterial infections.