Mechanisms of Drug Resistance in Tuberculosis and Potential Modulation Strategies

Tuberculosis (TB) is the 13th leading cause of death worldwide and the second leading cause of death after COVID-19 (above HIV and AIDS). The high rate of morbidity and mortality associated with this disease is due to the presence of multi-drug-resistant bacterial strains of Mycobacterium tuberculosis. Mechanisms of drug resistance for both first-line and second-line drugs are discussed. The existing limitations of these agents are also addressed in this chapter. To overcome these drug resistance mechanisms, several modulation strategies have emerged, such as carrying structural modifications in the existing drugs, targeting efflux pathways of various drugs, endurance of drug-inactivating enzymes, host-directed therapies (HDT), and so forth. The need of the hour is to understand and work on new strategies for combating resistance to anti-tubercular agents. The diverse range of technologies such as molecular biology, epidemiology, and bioinformatics requires working in a synchronous way to reduce the despair caused by such a lethal disease.