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High-Throughput 2018, 7(4), 31; https://doi.org/10.3390/ht7040031

Impact of Genomics on Clarifying the Evolutionary Relationships amongst Mycobacteria: Identification of Molecular Signatures Specific for the Tuberculosis-Complex of Bacteria with Potential Applications for Novel Diagnostics and Therapeutics

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada
Received: 6 August 2018 / Revised: 25 September 2018 / Accepted: 27 September 2018 / Published: 2 October 2018
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Abstract

An alarming increase in tuberculosis (TB) caused by drug-resistant strains of Mycobacterium tuberculosis has created an urgent need for new antituberculosis drugs acting via novel mechanisms. Phylogenomic and comparative genomic analyses reviewed here reveal that the TB causing bacteria comprise a small group of organisms differing from all other mycobacteria in numerous regards. Comprehensive analyses of protein sequences from mycobacterial genomes have identified 63 conserved signature inserts and deletions (indels) (CSIs) in important proteins that are distinctive characteristics of the TB-complex of bacteria. The identified CSIs provide potential means for development of novel diagnostics as well as therapeutics for the TB-complex of bacteria based on four key observations: (i) The CSIs exhibit a high degree of exclusivity towards the TB-complex of bacteria; (ii) Earlier work on CSIs provide evidence that they play important/essential functions in the organisms for which they exhibit specificity; (iii) CSIs are located in surface-exposed loops of the proteins implicated in mediating novel interactions; (iv) Homologs of the CSIs containing proteins, or the CSIs in such homologs, are generally not found in humans. Based on these characteristics, it is hypothesized that the high-throughput virtual screening for compounds binding specifically to the CSIs (or CSI containing regions) and thereby inhibiting the cellular functions of the CSIs could lead to the discovery of a novel class of drugs specifically targeting the TB-complex of organisms. View Full-Text
Keywords: mycobacterial genomes; comparative genomics; phylogenomics; tuberculosis-complex; novel drug targets; conserved signature indels; protein structures and surface loops; mycobacterial classification mycobacterial genomes; comparative genomics; phylogenomics; tuberculosis-complex; novel drug targets; conserved signature indels; protein structures and surface loops; mycobacterial classification
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Gupta, R.S. Impact of Genomics on Clarifying the Evolutionary Relationships amongst Mycobacteria: Identification of Molecular Signatures Specific for the Tuberculosis-Complex of Bacteria with Potential Applications for Novel Diagnostics and Therapeutics. High-Throughput 2018, 7, 31.

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