This prestigious lecture will be delivered as part of the conferral of the title of Doctor honoris causa by the University of Toulouse upon Dr. Manjula Reddy
Manjula Reddy
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, & Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
Bacterial Cell Walls
Peptidoglycan, a defining feature of the bacterial cell wall is crucial for the integrity and morphology of bacteria. Initially identified as a target of beta-lactam antibiotics, peptidoglycan has become a subject of much interest for its biology, its potential for the discovery of novel antibiotic targets, and its role in infection. It is a large net-like polymer made up of several glycan strands cross-linked through short peptides forming a scaffold around the bacterial cytosolic membrane. The significance of cross-link formation is known for decades as the beta-lactam antibiotics target the enzymes that catalyze this step. However, the importance of cross-link hydrolysis in peptidoglycan biology remained largely underappreciated. Recent studies from our lab have demonstrated the functions of cross-link cleavage in diverse physiological processes, including an indispensable role in peptidoglycan expansion during the cell cycle, thereby making cross-link cleaving enzymes an untapped target for novel drugs. Here, I will elaborate on the fundamental roles of cross-link specific peptidoglycan hydrolysis and its regulation in bacteria.
Selected publications
1. Chodisetti, PK., and Reddy, M. 2019. Peptidoglycan hydrolase of an unusual cross-link specificity contributes to bacterial cell wall synthesis. Proc Natl Acad Sci USA 116: 7825-7830
2. Bahadur, R., P.K. Chodisetti, and Reddy, M. 2021. Cleavage of Braun's lipoprotein Lpp from the bacterial peptidoglycan by a paralog of L,D-transpeptidases, LdtF. Proc Natl Acad Sci USA 118: 19
3. Som, N., and Reddy, M. 2023. Cross-talk between phospholipid synthesis and peptidoglycan expansion by a cell wall hydrolase. Proc Natl Acad Sci USA 120 (24), e2300784120
4. Rajguru, V., Chatterjee, S., Garde, S., and Reddy, M. 2024. Crosslink cleaving enzymes: the smart autolysins that remodel the bacterial cell wall. Trends in Microbiology doi: 10.1016/j.tim.2023.11.00
5. Kaul, M., Meher, SK., Nallamotu, KC., and Reddy, M. 2024. Glycan strand cleavage by a lytic transglycosylase, MltD contributes to the expansion of peptidoglycan in Escherichia coli. PLOS Genetics 20 (2), e1011161