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Study the role of acetylation in multidrug resistance of mycobacteria

Tuberculosis is a deadly infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the report of WHO, one-third of the world's population is infected with Mtb which causes millions of death annually worldwide. The increased incidence of multidrug resistance (MDR) of Mtb and its association with HIV infection turns tuberculosis into a global threat. Hence, it is an urgent need to explore the molecular mechanisms underlying the multidrug resistance in the pathogen. This knowledge may further lead to indentify the novel drug targets to treat the drug resistant Mtb. The primary causes of mycobacterial drug resistance have been attributed to the alternation of drug targets through mutation or due to the titration of the drugs by overproduction of the target. A number of reports suggested that efflux pumps play a critical role in development of drug resistance in mycobacteria. But it is not clearly understood that how these membrane transporter are in turn regulated in mycobacteria. It is conceivable that understanding the regulation of transporters will help us to better understand the drug resistance mechanism in mycobacteria. Lysine acetylation is one of the prevalent post-translational modifications of proteins that not only alters gene expression, but also can regulate mRNA stability, protein activity, and protein-protein interactions. Proteome wide lysine acetylation profile reveals that acetylation is involved in regulation of diverse cellular processes including central metabolism and protein synthesis in mycobacteria. Hence, we are investigating whether acetylation can regulate the activity of the membrane efflux transporters to develop drug resistance in mycobacteria.