Life Sciences & Biotechnology
Title : | Regulation of Survival, Dormancy and Resuscitation in Mycobacterium; Understanding the Role of Ribosome-Associated Factors |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Sandip Dey, Jadavpur University, West Bengal |
Timeline Start Year : | 2024 |
Timeline End Year : | 2026 |
Contact info : | sandip6bot@gmail.com |
Details
Executive Summary : | Mycobacterium tuberculosis affects 33% of the global population, with 1.8 billion people carrying latent infection. In latent infection, Mycobacterium cells alter their morphology and physiology to survive in low oxygen environments for decades. They can return to an active form and cause infection under immunocompromised conditions. Two DosR (dormancy survival regulon) regulated proteins, RafH and RafS, and HflX (a conserved GTPase), play a crucial role in maintaining dormant cell homeostasis by interacting with ribosomes and ribosomal subunits. RafH and RafS interact with ribosomes to create inactivated 70S ribosomes, while HflX splits vacant ribosomes into ribosomal subunits and imposes anti-association effects on both subunits. Mycobacterium cells slow down ribosomal RNA transcription, overall translation, and stabilize their ribosomes during dormancy. These methods include inactivation of ribosomes, promotion of specific mRNA translation, and stabilization of ribosomes. HflX, a known ribosome splitter, can restore ribosomes from inactive 100S dimers in Staphylococcus, but Mycobacterium imposes inactivation of ribosomes as 70S particles are not in 100S form. To withdraw inactivation effects, HflX should interact with RafH or RafS inactivated 70S ribosomes and split the complex to initiate translation. Recent studies have shown that Mycobacterium RafH and RafS bind near the decoding center of 30S subunit and prevent mRNA entry. The binding strategy of Mycobacterium HflX and ribosome or ribosomal subunits is not yet known. |
Organizations involved