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Vijay Srinivasan

Post-doctoral researcher

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.

Cell lengths of TB sensitive and resistant strains

M. tuberculosis under mid-log condition

M. tuberculosis under H2O2 isoniazid treatment and iron deficiency


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