Mycobacterium tuberculosis Molecular Determinants of Infection, Survival Strategies, and Vulnerable Targets

Abstract

Mycobacterium tuberculosis is the causative agent of tuberculosis, an ancient disease which, still today, represents a major threat for the world population. Despite the advances in medicine and the development of effective antitubercular drugs, the cure of tuberculosis involves prolonged therapies which complicate the compliance and monitoring of drug administration and treatment. Moreover, the only available antitubercular vaccine fails to provide an effective shield against adult lung tuberculosis, which is the most prevalent form. Hence, there is a pressing need for effective antitubercular drugs and vaccines. This review highlights recent advances in the study of selected M. tuberculosis key molecular determinants of infection and vulnerable targets whose structures could be exploited for the development of new antitubercular agents.

Keywords: Mycobacterium tuberculosis; antitubercular drugs; drug discovery; target identification; tuberculosis.

Figure 1

Visual summary, gene names, and structures of the molecular determinants of Mycobacterium tuberculosis infection described in the present review. From the upper left to upper right, in a counterclockwise fashion: enzymes involved in the biosynthesis of nucleotides, in inflammasome inhibition, DNA repair, and in the tricarboxylic acid (TCA) cycle, including the glyoxylate shunt. Abbreviations: OA, orotic acid; OPRT, orotate phosphoribosyltransferase; OMP, orotidine 5′-monophosphate; UMP, uridine monophosphate; IMP, inosine monophosphate; IMPDH, inosine 5′-monophosphate dehydrogenase; XMP, xanthosine monophosphate; GMP; guanosine monophosphate; R5P, Ribose 5-phopshate; PRPP, phosphorybosyl pyrophosphate; CS: citrate synthase; MDH: malate dehydrogenase; MS: malate synthase; ICL: isocitrate lyase. * Structure shown is of the Mycobacterium smegmatis PrsA homolog [8].