Prestigious Lecture by Dr. Manjula Reddy: Bacterial Cell Walls

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