Dr. Vijay Srinivasan Ph.D.
My research interest is mainly to investigate the molecular and cellular adaptations in Mycobacterium tuberculosis (M.tb) that contributes to its survival against host stress and antibiotics leading to clinical persistence and evolution. M.tb, the causative agent of tuberculosis, is able to survive antibiotic treatment in patients due to antibiotic resistance, but probably also due to antibiotic tolerance. Antibiotic tolerance in clinical M.tb isolates results in slow rate of antibiotic-mediated killing. The mechanisms leading to tolerance are poorly defined, although genetic mutations have also recently been implicated in enhancing tolerance. Antibiotic tolerance may lead to M.tb persistence during treatment and emergence of antibiotic resistant isolates, probably contributing to treatment failure.
I am investigating the antibiotic susceptibility differences between clinical M.tb isolates, such as difference in their minimum inhibitory concentration (MIC) of antibiotics and minimum duration of killing (MDK), the minimum concentration of antibiotics and the time required for killing 99% of the bacterial population post antibiotic exposure respectively. I will determine the level of antibiotic resistance and tolerance among clinical M.tb isolates under different host stress conditions. Phenotypic antibiotic resistance and tolerance will be investigated for genetic determinants by whole genome sequencing and genome wide association studies; as well as longitudinal M.tb isolates collected from TB patients will be investigated for emergence of genetic variants associated with antibiotic resistance and tolerance. The molecular mechanisms of genetic variants will be investigated by analyzing cellular and transcriptional adaptations. Influence of antibiotic resistance and tolerance mutations on treatment response in patients will be analyzed.
5 key recent research articles:
Rancoita, P. M., F. Cugnata, A. L. Gibertoni Cruz, E. Borroni, S. J. Hoosdally, T. M. Walker, C. Grazian, T. J. Davies, T. E. Peto, D. W. Crook, P. W. Fowler, D. M. Cirillo and CRyPTIC consortium (2018). “Validating a 14-Drug Microtiter Plate Containing Bedaquiline and Delamanid for Large-Scale Research Susceptibility Testing of Mycobacterium tuberculosis.” Antimicrob Agents Chemother 62(9). doi: 10.1128/AAC.00344-18
Vijay, S., H. T. Hai, D. D. A. Thu, E. Johnson, A. Pielach, N. H. Phu, G. E. Thwaites and N. T. T. Thuong (2017). “Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in Clinical Mycobacterium tuberculosis Isolates from Sputum, Oxidative Stress, and Iron Deficiency.” Front Microbiol 8: 2681. doi:10.3389/fmicb.2017.02681.
Vijay, S., D. N. Vinh, H. T. Hai, V. T. N. Ha, V. T. M. Dung, T. D. Dinh, H. N. Nhung, T. T. B. Tram, B. B. Aldridge, N. T. Hanh, D. D. A. Thu, N. H. Phu, G. E. Thwaites and N. T. T. Thuong (2017). “Influence of Stress and Antibiotic Resistance on Cell-Length Distribution in Mycobacterium tuberculosis Clinical Isolates.” Front Microbiol 8: 2296. doi:10.3389/fmicb.2017.02296.
Vijay, S., R. R. Nair, D. Sharan, K. Jakkala, N. Mukkayyan, S. Swaminath, A. Pradhan, N. V. Joshi and P. Ajitkumar (2017). “Mycobacterial Cultures Contain Cell Size and Density Specific Sub-populations of Cells with Significant Differential Susceptibility to Antibiotics, Oxidative and Nitrite Stress.” Front Microbiol 8: 463. doi: 10.3389/fmicb.2017.00463.
Vijay, S., M. Nagaraja, J. Sebastian and P. Ajitkumar (2014). “Asymmetric cell division in Mycobacterium tuberculosis and its unique features.” Arch Microbiol 196(3): 157-168. doi: 10.1007/s00203-014-0953-7.