Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Int J Mol Sci. 2019 Feb 27;20(5):1032. doi: 10.3390/ijms20051032.
In dealing with , the causative agent of the deadliest human disease-tuberculosis (TB)-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' genomic data affords an opportunity to explore and predict mycobacterial species' ability to utilize cholesterol employing 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 H37Rv on cholesterol, we predict that among 93 mycobacterial species, 51 species will be able to utilize cholesterol as a carbon source. This study'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.
在处理导致人类最致命疾病——结核病(TB)的病原体时,利用胆固醇作为碳源表明了使用胆固醇分解代谢基因/蛋白作为新型药物靶点的可能性。然而,关于分枝杆菌物种中胆固醇分解代谢的研究很少,并且能够利用胆固醇作为碳源的分枝杆菌物种的数量也未知。大量分枝杆菌物种基因组数据的可用性为利用 方法探索和预测分枝杆菌物种利用胆固醇的能力提供了机会。在这项研究中,通过推导全面的胆固醇分解代谢途径、开发用于提取同源蛋白数据的软件工具以及利用蛋白结构和功能数据,对 93 种分枝杆菌物种中的胆固醇分解代谢基因/蛋白进行了全面的比较分析。基于已证明或预测的与 H37Rv 在胆固醇上生长所必需或特异性相关的胆固醇分解代谢同源蛋白的存在,我们预测在 93 种分枝杆菌物种中,有 51 种能够利用胆固醇作为碳源。本研究的预测需要进一步的实验验证,结果应被视为分枝杆菌物种中胆固醇分解代谢及其相关基因/蛋白的信息来源。