Mycobacteria represent some of the deadliest bacterial pathogens known to humans. For example, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has afflicted mankind since the prehistoric era. Even in the age of modern medicine, treatment of TB entails a 6 to 9-month regimen of at least three specialized antibiotics. This is in sharp contrast to a short, mono-drug treatment for a typical bacterial infection. Today, TB is responsible for over a million deaths every year.
We study mechanisms underlying mycobacterial persistence against antibiotics. We use biofilms as a growth model in our studies. Biofilms are surface-associated, 3D-organized, multicellular communities of microbes. Most microbes, including mycobacteria, spontaneously form biofilms. We hypothesize that inherent heterogeneity in microenvironments of the biofilm architecture leads to the development of a specialized subpopulation of cells adapted to extreme nutritional and hypoxic stresses, and that these elite cells develop into persisters.
Our overarching goal is to define molecular targets of persister cells in mycobacterial biofilms. We believe that drugs against these targets will ultimately shorten the treatment regimen for TB.