Clinical Microbiology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India.
J Antimicrob Chemother. 2010 Aug;65(8):1694-701. doi: 10.1093/jac/dkq186. Epub 2010 Jun 4.
To evaluate the role of piperine as an inhibitor of Rv1258c of Mycobacterium tuberculosis.
Rifampicin, in combination with piperine, was tested against M. tuberculosis H37Rv and rifampicin-resistant (rif(r)) M. tuberculosis. A laboratory-generated rifampicin-resistant mutant (rif(r)) of M. tuberculosis was tested for drug susceptibility and the expression level of the putative efflux protein (Rv1258c) by real-time PCR. The three-dimensional (3D) structure of Rv1258c was also predicted using an in silico approach.
In the present study, rifampicin in combination with piperine, a trans-trans isomer of 1-piperoyl-piperidine, reduced the MIC and mutation prevention concentration (MPC) of rifampicin for M. tuberculosis H37Rv, including multidrug-resistant (MDR) M. tuberculosis and clinical isolates. Moreover, piperine effectively enhanced the bactericidal activity of rifampicin in time-kill studies and also significantly extended its post-antibiotic effect (PAE). In the presence of rifampicin, M. tuberculosis rif(r) showed a 3.6-fold overexpression of Rv1258c. The 3D structure of Rv1258c, using in silico modelling, was analysed to elucidate the binding of piperine to the active site.
The results of this study are suggestive of piperine's involvement in the inhibition of clinically overexpressed mycobacterial putative efflux protein (Rv1258c). Piperine may be useful in augmenting the antimycobacterial activity of rifampicin in a clinical setting.
评估胡椒碱作为结核分枝杆菌 Rv1258c 抑制剂的作用。
用利福平联合胡椒碱对结核分枝杆菌 H37Rv 及利福平耐药（rif(r)）结核分枝杆菌进行检测。采用实验室生成的结核分枝杆菌 rif(r)耐药突变株进行药物敏感性检测和实时 PCR 检测推测外排蛋白（Rv1258c）的表达水平。还采用计算方法预测 Rv1258c 的三维（3D）结构。
在本研究中，利福平联合胡椒碱（1-哌啶酰基-哌啶的反-反式异构体）降低了利福平对结核分枝杆菌 H37Rv 的 MIC 和防突变浓度（MPC），包括耐多药（MDR）结核分枝杆菌和临床分离株。此外，胡椒碱在时间杀伤研究中有效增强了利福平的杀菌活性，还显著延长了其抗生素后效应（PAE）。在利福平存在的情况下，结核分枝杆菌 rif(r) 中 Rv1258c 的表达水平增加了 3.6 倍。使用计算建模分析了 Rv1258c 的 3D 结构，以阐明胡椒碱与活性位点的结合。
本研究结果提示胡椒碱可能参与抑制临床过表达的分枝杆菌假定外排蛋白（Rv1258c）。胡椒碱可能有助于增强利福平在临床环境中的抗分枝杆菌活性。
