Life Sciences & Biotechnology
Title : | Biological role of protein persulfidation in Mycobacterium tuberculosis |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Mycobacterial Pathogenesis, Protein Persulfidation |
Principal Investigator : | Dr. Bhavna Maurya, Indian Institute Of Science, Bangalore, Karnataka |
Timeline Start Year : | 2024 |
Timeline End Year : | 2026 |
Contact info : | bhav.maurya20@gmail.com |
Details
Executive Summary : | Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is responsible for 30% of the world's population and 1.8 million deaths annually. Its success lies in its ability to establish chronic infection and persist in the host despite immune pressures and chemotherapy. Understanding persistence mechanisms is crucial for developing new therapeutic strategies against TB. Recent studies have shown the importance of sulfur metabolism, including the biosynthesis of hydrogen sulfide (H₂S) gas, in the persistence and drug resistance in Mtb. However, the mechanisms of H₂S biogenesis and its impact on Mtb physiology remain uncertain. In mammals, H₂S is generated primarily by three enzymes: cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE/MetB), and 3-mercaptopyruvate sulfurtransferase (MST). In vivo data using a Mtb CBS mutant did not show diminished H2S production. Another Mtb enzyme, cysteine desulfhydrase (Cds1, Rv3684), was reported to be a primary source of H₂S production in Mtb. The downstream influence of H₂S on various biological processes is mediated via a post-translational modification called protein-S-persulfidation (P-SSH) on cysteine residues (RSH). The genome analysis of Mtb showed four genes encoding proteins with rhodanese (TST) domains: cysA2, cysA3, sseA, and sseB. Preliminary data suggest that both CysA2 and SseB carry out canonical 3-MST reaction using 3-mercaptopyrvuate as the substrate in vitro. |
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