Life Sciences & Biotechnology
Title : | Deciphering the role of "LexA family transcriptional regulator" in SOS induced mutagenesis and antimicrobial resistance (AMR) of multi-drug resistant Acinetobacter baumannii |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Saravanan Matheshwaran, Indian Institute Of Technology Kanpur (IITK), Uttar Pradesh |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | saran@iitk.ac.in |
Details
Executive Summary : | Stress response in bacterial species is induced by DNA-damaging agents, leading to the error-prone mutagenic "SOS" response pathway. LexA and RecA are key players in regulating the global network of stress-responsive and damage-repair genes involved in the SOS response. Under normal conditions, LexA transcriptionally represses all SOS-regulated genes, enabling bacteria to survive DNA damage and acquire antimicrobial resistance through mutagenesis. In Acinetobacter baumannii, a NO LexA homolog has been identified, indicating that non-canonical SOS mechanisms are being established. UmuDAb, an analogue of canonical LexA, controls only genes associated with error-prone DNA polymerase V. The regulation of other genes responsible for DNA damage repair and stress response remains unclear in A. baumannii. Understanding the function of an uncharacterized LexA-like protein, the LexA family transcriptional regulator protein, may provide insight into the regulatory network of SOS-mutagenesis and the induction of antimicrobial resistance. A multi-drug resistant A. baumannii IITK SM3 strain, characterized by 19 antibiotic resistance genes (ARGs) and 6 unique ARGs found exclusively in the strain, poses a serious threat to mankind.
The proposed study aims to characterize the new strain and understand LexA-mediated SOS response in multidrug resistant A. baumannii IITK SM3. Acquired knowledge on LexA-regulated SOS response will open a new avenue to design novel antibiotics that can elude AMR. Key questions addressed include how the multidrug-resistant A. baumannii IITK SM3 strain acquired ARGs, how the newly identified LexA-family transcription factor regulates SOS response, adaptive mutagenesis, and AMR in A. baumannii IITK SM3, the components of LexA-Regulated SOS response, and any cross-talk between UmuDAb regulated pathway and LexA regulated pathway. |
Total Budget (INR): | 45,87,264 |
Organizations involved