Persistence and Antibiotic Tolerance in Mycobacteria
Speaker: Deborah Hung, Broad Institute of MIT and Harvard - Massachusetts General Hospital
Department: Chemical & Biological Engineering
Location: Engineering Quadrangle A224
Date/Time: Wednesday, November 28, 2012, 4:00 p.m. - 5:00 p.m.
Tuberculosis continues to be a disease of significant morbidity and mortality. Complicating its management are its diverse manifestations, ranging from acute disease to latent infection. It is estimated that 1/3 of the worlds population has latent TB, resulting in an enormous reservoir from which reactivation to acute disease can occur. More effective drugs are urgently needed to simplify and shorten treatment courses in order to address the challenges of compliance to the requisite lengthy courses required for sterilization and cure.
During both active and latent infection, it has been proposed that a population or subpopulation of bacteria enters a reversible non-replicating state, refractory to traditional antibiotics. The term phenotypic antibiotic tolerance (drug tolerance) is used to describe the reduced efficacy of antibiotics against these bacteria in the absence of genotypic resistance. In Mtb, it has been proposed that in vivo drug tolerance could explain the persistence of infection in the face of prolonged therapy. Thus, integrating our understanding of drug tolerance and the basis for bacterial survival in the face of chemotherapy into therapeutic discovery could be key to designing new strategies for targeting latent and persistent infection. We have been using chemical biological approaches to studying persistence and drug tolerance in order to understand the physiology of bacteria refractory to antibiotic killing and to inform new approaches to managing infection.