Life Sciences & Biotechnology
Title : | The role of mistranslation in driving antibiotic tolerance and resistance |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Antibiotic Resistance Mechanisms |
Principal Investigator : | Dr. Laasya Samhita, Ashoka University, Sonipat, Haryana |
Timeline Start Year : | 2024 |
Timeline End Year : | 2026 |
Contact info : | laasya2@gmail.com |
Details
Executive Summary : | Antimicrobial resistance (AMR) is a growing concern, with mutation-driven resistance being the main focus. Mistranslation, or errors in protein synthesis, is responsible for protein sequence diversity in living cells and has been linked to antibiotic tolerance and resistance. Mistranslation generates non-heritable variation and is often thought to be short-term and environment-driven. Recent research shows that mistranslation alters mutational paths under antibiotic selection, suggesting it can influence antibiotic resistance evolution. To investigate the interaction of wild type bacterial mistranslation rates with tolerance and resistance upon antibiotic exposure, researchers propose establishing a single cell mistranslation system using a genomically integrated GFP reporter. They will track the influence of antibiotics on mistranslation rates and understand the propagation and spread of natural mistranslation in wild type E. coli cells. Experimental evolution regimes will be used to understand the population level impact of altered translation rate and accuracy on adaptation to antibiotics. The failure of bactericidal antibiotics is a major problem today, and mistranslation is associated with the development of antibiotic resistance. Environmental exposure to sub-MIC antibiotic concentrations is likely to reduce protein synthesis rates, potentially reducing antibiotic dosages. The effect of altered translation rate on antibiotic action and secondary non-essential drug target identification will be explored.
In the short term, increasing translation accuracy can inhibit resistance to ciprofloxacin. If this holds in the evolution regime, a drug adjuvant administered with fluoroquinolones can generate hyper-accurate ribosomes and block resistance development. |
Total Budget (INR): | 29,24,370 |
Organizations involved