Targeting amino acid metabolism of Mycobacterium tuberculosis for developing inhibitors to curtail its survival

Abstract

Tuberculosis caused by the bacterium, Mycobacterium tuberculosis (Mtb), continues to remain one of the most devastating infectious diseases afflicting humans. Although there are several drugs for treating tuberculosis available currently, the emergence of the drug resistant forms of this pathogen has made its treatment and eradication a challenging task. While the replication machinery, protein synthesis and cell wall biogenesis of Mtb have been targeted often for anti-tubercular drug development a number of essential metabolic pathways crucial to its survival have received relatively less attention. In this context a number of amino acid biosynthesis pathways have recently been shown to be essential for the survival and pathogenesis of Mtb. Many of these pathways and or their key enzymes homologs are absent in humans hence they could be harnessed for anti-tubercular drug development. In this review, we describe comprehensively the amino acid metabolic pathways essential in Mtb and the key enzymes involved therein that are being investigated for developing inhibitors that compromise the survival and pathogenesis caused by this pathogen.

Keywords: amino acids; arginine; pranlukast; quinolones; tuberculosis.