Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India; Interdisciplinary Biotechnology Unit, Aligarh Muslim University Aligarh, 202002, India.
Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India.
Microb Pathog. 2018 Aug;121:179-183. doi: 10.1016/j.micpath.2018.05.034. Epub 2018 May 23.
Failure of multi drug resistant tuberculosis (MDR-TB) treatment has increased the risk of aminoglycosides resistance, disease transmission, morbidity and mortality. Aminoglycosides are commonly used in multi drug resistant tuberculosis (MDR-TB) treatment. They inhibit protein synthesis by interacting with translationary steps. Apart from gene mutations various mechanisms of aminoglycosides resistance have been reported but still our knowledge regarding aminoglycosides resistance is fragmentary. Proteomics and bioinformatics approaches are the most accepted approaches to explore the unrevealed mechanisms of aminoglycosides resistance. Our previous studies suggested that over expression of Rv0148 in aminoglycosides resistant M. tuberculosis clinical isolates potentially leads to aminoglycosides resistance. In this study we have analyzed the protein-protein interactions of putative short-chain type dehydrogenase/reductase (Rv0148) and predicted the proteins target linked to the aminoglycosides drug resistance. Interactome predicted that fatty acid synthase (fas), dehydrogenase (htdY), dehydrogenase (MT3642), quinine oxidoreductase (MT0157), phenyloxazoline synthase (mbtB), hypothetical protein (Rv0130), 3-oxoacyl-ACP synthase (kasA), 3-oxoacyl-ACP synthase (kasB) aldehyde dehydrogenase (MT0155) and hypothetical protein (Rv1867) were the interactive partners of Rv0148. We have suggested that Rv0148, its predictive interactive protein partners and their pathways (via lipid metabolism as well as intermediary metabolism and respiration) cumulatively unlock the mystery of aminoglycosides resistance in M. tuberculosis.
耐多药结核病（MDR-TB）治疗失败增加了氨基糖苷类耐药、疾病传播、发病率和死亡率的风险。氨基糖苷类药物常用于耐多药结核病（MDR-TB）的治疗。它们通过与翻译步骤相互作用来抑制蛋白质合成。除基因突变外，还报道了各种氨基糖苷类耐药机制，但我们对氨基糖苷类耐药的了解仍然是零散的。蛋白质组学和生物信息学方法是探索未揭示的氨基糖苷类耐药机制的最被接受的方法。我们之前的研究表明，在氨基糖苷类耐药的结核分枝杆菌临床分离株中，Rv0148 的过度表达可能导致氨基糖苷类耐药。在这项研究中，我们分析了假定的短链型脱氢酶/还原酶（Rv0148）的蛋白质-蛋白质相互作用，并预测了与氨基糖苷类药物耐药相关的蛋白质靶标。相互作用组预测脂肪酸合酶（fas）、脱氢酶（htdY）、脱氢酶（MT3642）、奎宁氧化还原酶（MT0157）、苯并恶唑啉合酶（mbtB）、假定蛋白（Rv0130）、3-氧酰基-ACP 合酶（kasA）、3-氧酰基-ACP 合酶（kasB）醛脱氢酶（MT0155）和假定蛋白（Rv1867）是 Rv0148 的相互作用伙伴。我们提出，Rv0148、其预测的相互作用蛋白伙伴及其途径（通过脂质代谢以及中间代谢和呼吸）共同揭示了结核分枝杆菌中氨基糖苷类耐药的奥秘。
