Comparative Genomics Of Mycobacteria: Identification Of Novel Anti-Tubercular Drug Targets

Abstract

Mycobacteria are aerobic, unicellular, highly pathogenic organisms, responsible for lethal diseases in humans and other animals. One of the most investigated of the Mycobacteria is Mycobacterium tuberculosis (M. tuberculosis), a deadly pathogen causing tuberculosis in humans, a continuously growing threat to mankind. The development of multidrug-resistant, extensively drug-resistant, and totally drug-resistant strains of M. tuberculosis, combined with the scarcity of new drug targets, suggests that new research is needed to explore the biology of M. tuberculosis to investigate new therapeutic measures against tuberculosis and set forth novel potential drug targets. The genome sequence of M tuberculosis has been available for a while now on public databases, and a genome-based method can be used to help understand the adaptation/evolution of this pathogen. Comparative genomics provides us with the opportunity to attempt to understand the mechanism of pathogenesis, including pathways and functions shared among species, and also the physiologic differences, which can help address the pathogenic properties of M. tuberculosis. Comparing the genome of the pathogenic M.tuberculosis to that of a non-pathogenic mycobacterium, e.g. M. vanbaalenii, can shedsome light on what unique characteristic it is that makes M. tuberculosis more virulent and prone to developing resistance. Recognising any such uniqueness that can possibly be a drug target may ultimately lead to the development of a new drug in the fight against tuberculosis. This study was performed to see if the use of comparative genomics can be used to identify unique genes that can possibly become novel drug targets. The whole genomes of 8 mycobacterial species belonging to six different niches (M. tuberculosis H37Rv, M.africanum GM041182, M. bovis AF2122/97, M. abscessus ATCC 19977, M. avium 104, M. leprae TN, M. marinum, and M. vanbalenii) were downloaded from TB database and compared using BLAST software. Genes unique to each of the species were identified. The genome comparison of 8 different mycobacterial species belonging to 6 different niches revealed 200 genes unique to M. tuberculosis H37Rv. The uniqueness of 200 genes identified for M. tuberculosis H37Rv by genome comparison were further investigated by comparing the genes with available amino acid sequences to the genomes of 96 mycobacterial species. Functional classification of these genes was done using genome mapping with each of these genes with 5 upstream and 5 downstream proteins. The study results indicated that genome comparison is a viable method to identify unique genes that in the quest to identify novel potential drug targets.