Comparative analyses of the proteins from Mycobacterium tuberculosis and human genomes: Identification of potential tuberculosis drug targets

• Protein sequences from 23 M.tb genome strains and Homo sapiens compared
• 1,478 ‘conserved’ M.tb proteins absent in human identified
• 94 interacting M.tb proteins prioritized as potential new TB targets for validation.
• 10 ‘druggable’ TB targets with known drugs identified
• Prediction of drug targets using bioinformatics depends upon methods and datasets used.

Tuberculosis, one of the major infectious diseases affecting human beings is caused by the bacillus Mycobacterium tuberculosis. Increased resistance to known drugs commonly used for the treatment of tuberculosis has created an urgent need to identify new targets for validation and to develop drugs. In this study, we have used various bioinformatics tools, to compare the protein sequences from twenty-three M. tuberculosis genome strains along with the known human protein sequences, in order to identify the ‘conserved’ M. tuberculosis proteins absent in human. Further, based on the analysis of protein interaction networks, we selected one-hundred and forty proteins that were predicted as potential M. tuberculosis drug targets and prioritized according to the ranking of ‘clusters’ of interacting proteins. Comparison of the predicted 140 TB targets with literature indicated that 46 of them were previously reported, thereby increasing the confidence in our predictions of the remaining 94 targets too. The analyses of the structures and functions corresponding to the predicted potential TB drug targets indicated a diverse range of proteins that included ten ‘druggable’ targets with some of the known drugs.