Mary Nantongo, MS
Repurposing ß-Lactam Antibiotics for Tuberculosis Treatment
Abstract
Tuberculosis (TB) remains a major global health threat. Drug-resistant strains, including MDR-TB and XDR-TB, limit treatment options, with current therapies being prolonged, toxic, and less effective. Resistance is being reported for even the new drugs like bedaquiline, undermining drug discovery programs. ß-lactam (BL) antibiotics, widely used for bacterial infections, are underutilized in TB treatment due to Mtb’s ß-lactamase (BlaC), which hydrolyzes them. Recently, dual BL therapy or BL/ß-lactamase inhibitor (BLI) combinations have proven to overcome this resistance. This study investigates dual BL and BL/BLI combinations by; assessing their in vitro efficacy, structure-activity relationships with peptidoglycan enzymes, and intracellular activity against Mtb-infected macrophages. With susceptibility testing, enzyme kinetics, molecular docking, and X-ray foot printing, we hope to provide mechanistic insights, positioning BL for TB treatment and advancing drug discovery for MDR-TB.
I'm excited to receive this fellowship, which fuels my mission to advance innovative TB drug discovery. It reinforces my belief that impactful science can change lives and brings me one step closer to serving the communities that need it most.
