Infants and young children are at the greatest risk for Mycobacteria infections. Mycobacterial infections can be highly persistent and tolerant to antimicrobials. Mycobacterial biofilms harbor a drug-tolerant “persister “population, which is similar to what is observed during infection in humans and thus serves as a model of persistent bacteria. We have recently identified small molecules (termed MBIs) that inhibit biofilm formation by M. tuberculosis and M. abscessus—two pathogens relevant to infant and child health.
Aims: 1) Investigate the effect of MBI treatment on persister formation, stress tolerance, and pathogenesis; 2) Identify more potent MBIs against biofilm formation and persister formation; 3) Characterize MBI-targeted proteins and their roles in mycobacterial disease and antibiotic tolerance
Potential impact: These studies will expand knowledge of pathways involved in mycobacterial pathogenesis and contribute to the development and optimization of novel chemotherapeutic strategies to treat pediatric mycobacterial infections.