Molecular insights on the persistence of Mycobacteria
Author and Affiliations
1. First author : Hemant Joshi
Affiliations: Laboratory of molecular biology and genetic engineering, School of biotechnology. Jawaharlal Nehru University, New Delhi, India.; 2. Co-corresponding author : Prof. Nirupma Banerjee; Affiliations: Laboratory of molecular biology and genetic engineering, School of biotechnology. Jawaharlal Nehru University, New Delhi, India;
3. Corresponding author: Prof. Rakesh Bhatnagar
Affiliations: Laboratory of molecular biology and genetic engineering, School of biotechnology. Jawaharlal Nehru University, New Delhi, India.
Abstract
To control M. tuberculosis infection prolonged chemotherapy is recommended. A small population of cells escape from the lethal effects of the drugs either by acquiring drug resistance or by switching to a quiescent state with low metabolic activity. The latter population is antibiotic tolerant and remains dormant in the host. These are termed as persisters and are responsible for reactivation of the disease under conditions conducive for their growth. New approaches are required to understand and kill the persisters for effective eradication of the bacilli from the host. M. tuberculosis has evolved to endure intracellular as well as extracellular hostile environments such as antibiotics, oxidative stress, pH stress and nutrient starvation etc. The underlying mechanisms of bacterial persistence are poorly understood and the key determinants are also not well defined. Therefore, we have undertaken this study to elucidate the molecular basis of persistence. Using transposon mutagenesis as a tool, we have identified mutants defective in parameters likely to be involved in the epigenetic regulation of persistence. We present data using different antibiotic screens for the isolation of mutants of M. smegmatis as model, in this study. In conclusion, we hypothesize that our approach will provide novel insights into the mechanisms of persister formation and survival of mycobacteria, revealing new target for the development of persister directed antibiotics.