Drug-Resistant Tuberculosis: Development Mechanisms and Methods of Molecular Genetic Diagnosis

Abstract

The widespread occurrence of drug-resistant tuberculosis is an important public health challenge. To better understand this phenomenon, the article summarizes current ideas on the development of mechanisms of Mycobacterium tuberculosis resistance to antituberculosis drugs. Special attention is paid to the mechanism of acquired resistance based on mutations in the genes encoding antituberculosis drug targets or enzymes that translate pro-drug into its active form; the effect of these mutations on fitness of the pathogen is in the focus of the article. It emphasizes the leading role of molecular genetic methods for diagnosing M. tuberculosis drug resistance and importance of these methods for preventing the expansion of the pathogen’s resistance range and the spread of resistant clones in the population. A comparison of sequencing and PCR-based methods capacities led to a conclusion that at the current stage of technological development it is reasonable to use each of these approaches for specific purposes: domestic PCR-based tests — for diagnosis, and sequencing — for basic research of M. tuberculosis evolution and epidemiological monitoring. Promising areas of M. tuberculosis resistance research were proposed to develop new approaches for diagnosis and treatment of drug-resistant tuberculosis and to provide effective personalized therapy.