Drug resistance in Mycobacterium tuberculosis: An evolutionary perspective and its adaptation to the lung microenvironment

A highly specialized airborne human intracellular pathogen, Mycobacterium tuberculosis (Mtb), causes the disease tuberculosis (TB), with one death per second and approximately 10 million cases per year worldwide. Mtb has emerged as a health risk due to its ability to adapt to drugs. The emergence of drug-resistant Mtb is affected by factors such as drug-resistant gene mutations, the efficacy of TB treatment, genetic background of the strain, and its ability to adapt to host and specific environmental conditions. Mutations in gene coding for drug targets are the evident reason for drug resistance and are believed to arise mainly through single-step chromosomal mutations, single nucleotide polymorphisms (SNPs), and insertion-deletions. Stepwise fixation of mutations leads to acquired drug resistance, resulting in the gradual development of multiple types of drug-resistant Mtb strains. Approximately 25 % of the world population demonstrates some level of immunological response against Mtb infection that may remain dormant (TB infection) or develop into active disease (TB disease). The interaction of Mtb with the host during the early stages of infection can influence the disease outcome, driving the development of active, latent, or resistant TB. The adaptation of bacterial strains in the lung environment during the course of infection depends on their dynamic and unique cell envelope, their composition and metabolic responses in drug-resistant strains. Drug-susceptible and drug-resistant bacteria will adapt to the lung environment in distinct ways. In this review, we have explored the evolution of drug-resistant strains and their adaptation to the changing lung environment.