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Anil K. Ojha, Ph.D.
We study the molecular basis of persistence of one of the deadliest bacterial pathogens, Mycobacterium tuberculosis (Mtb), which kills over million people every year. Mtb is the causative agent of human tuberculosis (TB), which has inflicted mankind since the prehistoric era. But even in the age of modern medicine, the only possible treatment of TB is a 6-9 month regimen of three specialized anti-TB antibiotics. This lengthy and complicated regimen is in sharp contrast to the week long, mono-drug treatment for most other bacterial infections.
We are focused on addressing unmet challenges in TB control. Our investigations are addressing questions like; a) What makes M. tuberculosis the toughest of all bacterial species, with an ability to tolerate virtually all kinds of stress? and b) How we can shorten the TB treatment? In one of our projects, we are testing a hypothesis that the extraordinary persistence of M. tuberculosis against antibiotics is facilitated by the pathogen’s ability to grow in organized multicellular structures, called biofilms.
We have developed various molecular tools to visualize the location of drug tolerant persisters inside the biofilms, and using these tools we are asking as to how localization and frequency of these persisters are perturbed in vitro and in animal models in genetically defined mutants of biofilms.
In another project we are investigating the significance of cell envelope remodeling enzymes, lipid hydrolases, in mycobacterial resilience against host-derived stresses. Our particular focus is on trehalose dimycolate hydrolase (TDMH), which modulates the envelope permeability of Mtb in intracellular environment and subsequently balances the overall growth in host-responsive manner.
Finally, we strive to translate the findings from the laboratory into clinical application. For example, we discovered lysis of Mtb by exogenous TDMH and we are currently testing the use of this enzyme in efficient release of DNA for PCR-based diagnosis of TB.