Proteomics and Bioinformatics: A Modern Way to Elucidate the Resistome in Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) remains one of the world’s biggest threats which are caused by Mycobacterium tuberculosis. According to WHO 2016 report, 10.4 million people were infected worldwide with 1.8 million deaths including 0.4 million individuals with HIV-TB coinfection [1]. Vaccines, diagnostics and drugs are the available current tools to control this situation. Over the half century, Mycobacterium bovis bacille Calmette Guérin (BCG) is still the only vaccine against TB worldwide, despite showing highly variable efficacy (0–80%) in different trials [2]. Worldwide, sputum smear microscopy and culture remains the commonly used TB diagnostic and gold standard method respectively. However, use of rapid molecular testing like Line Probe Assay (LPA) has been used for detection of Rifampicin and isoniazid drug resistant Mycobacterium tuberculosis strains. Recently in India, Revised National TB Control Programme (RNTCP) has approved a study for the Validation of second line LPA for detecting resistance to fluoroquinolones, aminoglycosides (kanamycin, amikacin) and cyclic peptides (capreomycin). First and second line anti-TB drugs are effective and necessary component of short course chemotherapy. The treatment failure can lead to the emergence of resistant strains [Multidrug-resistant Tuberculosis (MDR-TB), Extensively Drug Resistant Tuberculosis (XDR-TB) and Totally Drug Resistant Tuberculosis (TDR-TB)] and consequently spread of the resistant form of the disease which have worsened the situation and became a major threat to community. The reasons for this are complex and multifactorial. These drug resistant M. tuberculosis strains or bad bugs can resist the action of drugs by the various mechanisms. These includes target gene mutations [3], drug modifying enzymes [4], over expression of efflux pumps and porins alterations [5,6], drugs trapping and overexpression of proteins showed drug neutralizing effects [7-13]. Majorly of drug resistance is contributed by target gene mutation however remaining part of drug resistance is due to various other mechanisms. Our existing gadgets (vaccines, diagnostics and therapeutics) are incapable to provide the complete protection against these deadly situations.