Comprehensive Comparative Analysis of Cholesterol Catabolic Genes/Proteins in Mycobacterial Species

• Main Authors: Rochelle van Wyk, Mari van Wyk, Samson Sitheni Mashele, David R. Nelson, Khajamohiddin Syed
• Format: Article
• Language: English
• Published: MDPI AG 2019-02-01
• Series: International Journal of Molecular Sciences
• Subjects: Cholesterol catabolism; Cholesterol catabolic genes/proteins; Comparative analysis; in silico analysis; <i>Mycobacterium tuberculosis</i>; <i>Mycobacterium tuberculosis</i> complex; Tuberculosis; <i>Mycobacterium chelonae-abscessus</i> complex; <i>Mycobacterium avium</i> complex; Mycobacteria causing leprosy; Non-tuberculous mycobacteria; Saprophytes; Software tool
• Online Access: https://www.mdpi.com/1422-0067/20/5/1032

In dealing with <i>Mycobacterium tuberculosis</i>, the causative agent of the deadliest human disease&#8212;tuberculosis (TB)&#8212;utilization of cholesterol as a carbon source indicates the possibility of using cholesterol catabolic genes/proteins as novel drug targets. However, studies on cholesterol catabolism in mycobacterial species are scarce, and the number of mycobacterial species utilizing cholesterol as a carbon source is unknown. The availability of a large number of mycobacterial species&#8217; genomic data affords an opportunity to explore and predict mycobacterial species&#8217; ability to utilize cholesterol employing <i>in silico</i> methods. In this study, comprehensive comparative analysis of cholesterol catabolic genes/proteins in 93 mycobacterial species was achieved by deducing a comprehensive cholesterol catabolic pathway, developing a software tool for extracting homologous protein data and using protein structure and functional data. Based on the presence of cholesterol catabolic homologous proteins proven or predicted to be either essential or specifically required for the growth of <i>M. tuberculosis</i> H37Rv on cholesterol, we predict that among 93 mycobacterial species, 51 species will be able to utilize cholesterol as a carbon source. This study&#8217;s predictions need further experimental validation and the results should be taken as a source of information on cholesterol catabolism and genes/proteins involved in this process among mycobacterial species.