We study mechanisms underlying mycobacterial persistence against antibiotics. We use biofilms as a growth model in our studies. Biofilms are formed by most microbes including mycobacteria, and are defined as surface-associated, 3D-organized, multicellular communities encapsulated by extracellular matrix. We hypothesize that inherent heterogeneity in microenvironments of biofilms 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. For example, we have observed that zinc depletion in mycobacterial biofilms induce ribosome hibernation, leading to the development of drug tolerant persister cells.
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Infections with Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB) in humans, are difficult to eradicate with antibiotics: a 6-month long multidrug regimen is necessary for the treatment of TB. The drug recalcitrance of TB infections has been associated with...read more