Cluster analysis of selected Mycobacterium species using rifampicin resistance DNA-directed RNA polymerase beta subunit (rpoB) gene

Abstract

Background: Rifampicin is an important drug being one of the first line of drug combination for tuberculosis (TB). Multidrug resistance tuberculosis is a major global health threat in view of the danger it poses to the treatment and control of TB. Rifampicin targets the β-subunit RNA polymerase encoded by the rpoB gene of mycobacteria, thereby inhibiting transcription and, therefore, stopping translation. Mycobacteria with a mutated rpoB gene are resistant to rifampicin effect. In the present study, sequences of rpoB gene of 7 common species of Mycobacterium were used for cluster analysis in order to assess genetic diversity in the bacteria. This was based on the premise that rpoB gene diversity assessment in Mycobacterium spp. may influence rpoB-based drug design in possible cases of co-infection with two or more Mycobacterium spp. Objective: To identify wide spectrum drug target for solving the problem of rifampicin resistance in mycobacteria. Methods and materials: Relevant papers were obtained from literature databases mainly PubMed (www.ncbi.nlm.nih.gov/pubmed/), PubMed Central or PMC (www.ncbi.nlm.nih.gov/pmc) and other sources including Google scholar. Sequences of the Mycobacteria spp. retrieved from Mycobacterium web database platform and MSA performed using MEGA-X softwafre. Results: The results revealed general low gene diversity in Mycobacterium giving 2 main clusters: M. tuberculosis, M. bovis, M. leprae, M. lepromatosis, and M. marium clustered together while M. smegmatis and M. abscessus formed another cluster. Amino acid sequence analysis of rpoB protein sequences indicated more diversity when compared to rpoB gene sequences resulting in a 3-cluster tree. Protein cladogram gave three clusters: M. tuberculosis and M. bovis; M. leprae and M. lepromatosis; M. smegmatis and M. abscessus. M. marinum was simplicifolious. Conclusion: The results of the present bioinformatics analysis suggested that an rpoB gene-targeted drugs might be more effective than protein-targeted drugs in cases of co-infection with Mycobacterium species pathogenic to human.