Vivian Bui Rose Hills
MmpL Transporters in M. abscessus Virulence and Impermeability
Incidence and deaths due to non-tuberculous mycobacteria (NTM) have been increasing globally, in part due to their intrinsic drug resistance. Mycobacterium abscessus (Mabs) is a pathogenic and clinically challenging NTM species, causing devastating pulmonary disease and tissue infection. Drug resistance of Mabs partly results from its unique mycomembrane, which is a formidable permeability barrier. While the inner leaflet primarily consists of mycolic acids, the outer leaflet is poorly characterized. Some mycobacterial membrane protein Large (MmpL) transporters export lipid components of the mycomembrane, but the substrates and functions of most MmpLs remain unknown. The high number of MmpLs in Mabs leads to questions about each MmpL’s function as a lipid transporter or drug efflux pump, as well as its contribution to virulence and antibiotic resistance. My project will investigate each MmpL’s role in these important traits. I will create MmpL knockouts and test the mutants to evaluate each MmpL’s function in antibiotic resistance and pathogenesis. This project will help elucidate barriers for anti-NTM antibiotics and chemotherapeutic agents to enter the bacterial cytoplasm.