A Comprehensive Review on<i>Mycobacterium tuberculosis</i>Targets and Drug Development from a Structural Perspective

Mycobacterium tuberculosis (Mtb) is the most effective pathogen of mankind and is second only to human immunodeficiency virus/AIDS as the greatest cause of death worldwide due to a single infectious agent. Antibiotic resistance is a major reason why Tuberculosis (TB) is so difficult to eradicate and has become a challenge to overcome. Besides drug resistance, another major problem directly arises from the combination of Mtb physiology and human immune response. The Mycobacterium genus belongs to the GC-rich Gram-positive Actinobacteria phylum, order of Actinomycetales, and suborder of Corynebacterineae that also includes the Corynebacterium and Nocardia genera. Although the TB drug development pipeline also has promising candidates in the early stages, there is a clear gap between early preclinical development. Besides a factors, control of gene expression by the Mtb RNA polymerase is mediated by various regulatory proteins that represent promising targets in the treatment of mycobacterial infections.