Mycobacterial Metabolic Pathways as Drug Targets: A Review

Abstract

Mycobacterium is acid fast genus of bacteria that include many pathogenic and non pathogenic species. Treatment is made quite difficult by the presence of metabolically silent, persistent or dormant bacteria within host lesions, which are not susceptible to the anti-mycobacteria drugs that usually kill growing bacteria but not persistent mycobacteria. The emergence of antibiotic resistance strains has raised the need towards the development of new antibiotics or drug molecules which can kill or suppress the growth of pathogenic Mycobacterium species. Novel efforts in developing drugs that target the intracellular metabolism of M. tuberculosis often focus on metabolic pathways that are specific to mycobacterium. Potential drug targets were also identified from pathways related to lipid metabolism, carbohydrate metabolism, amino acid metabolism, energy metabolism, vitamin and cofactor biosynthetic pathways and nucleotide metabolism. The objective this paper was to review those mycobacterium metabolic pathways as drug target and the problems of current TB drugs. The crucial problems of current TB therapy are development of multi-drug resistance and inefficiency of current TB drug to kill or inhibit non growing mycobacterium. The identification of drug target from that unique metabolism of mycobacterium is crucial to develop new drug for persistent and latent infection of tuberculosis. Despite an urgent need for new therapies targeting persistent bacteria, our knowledge of bacterial metabolism throughout the course of infection remains rudimentary. Therefore, better understanding on the physiology of mycobacterium during the latent period will help in the identification of new drug targets that can act on the persistent mycobacterium. Identification of these targets will to produce new drugs against tuberculosis that will overcome the limitations of existing drugs such as, prolonged chemotherapy, failure against persistent infection and multidrug resistance.

Keywords: Anti-tuberculosis agent, Drug targets, Metabolic pathway, Mycobacterium