Mechanisms of Drug Resistance in Mycobacterium tuberculosis

Drug resistance in tuberculosis (TB) is a particular problem because the lengthy therapy of at least 6 months makes patient compliance very difficult, which frequently creates drug-resistant strains of Mycobacterium tuberculosis . This chapter provides an update on genes associated with drug resistance and the current understanding of mechanisms of drug resistance and drug action in M. tuberculosis . The emergence of drug resistance in bacteria is one of the easiest demonstrations of the "survival of the fittest" concept of Darwin's theory of evolution. Resistance is thus due to a change in the genotype resulting in a drug-resistant phenotype of a bacterium, which can be passed on to subsequent generations. This is in contrast to tolerance, or phenotypic resistance, another phenomenon that is common to M. tuberculosis and other bacterial species, in which changes in the metabolic or physiological status of the cell induce temporary drug resistance as seen in stationary-phase, starved, or dormant bacteria. Knowledge about the mutations conferring drug resistance not only leads to understanding of the mechanisms of drug resistance and drug action but also facilitates rapid detection of drug resistance by molecular means. Phenotypic resistance is a major problem for antibiotic therapy, especially for TB. Nongrowing bacteria can be divided roughly into two different types depending on whether they grow immediately on subculture into a defined fresh medium.