Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis
IR@IIIM: CSIR-Indian Institute of Integrative Medicine, Jammu
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| Title |
Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis
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| Creator |
Sharma, S.
Kumar, M. Sharma, S. Nargotra, A. Koul, S. Khan, I. A. |
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| Subject |
Pharmacological Sciences
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| Description |
Objectives: To evaluate the role of piperine as an inhibitor of Rv1258c of Mycobacterium tuberculosis.
Methods: Rifampicin, in combination with piperine, was tested against M. tuberculosis H37Rv and rifampicinresistant
(rifr) M. tuberculosis. A laboratory-generated rifampicin-resistant mutant (rifr) 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.
Results: 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 rifr 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.
Conclusions: 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.
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| Date |
2010
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://iiim.csircentral.net/310/1/10.1093jacdkq186.pdf
Sharma, S. and Kumar, M. and Sharma, S. and Nargotra, A. and Koul, S. and Khan, I. A. (2010) Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis. Journal of Antimicrobial Chemotherapy, 65 (8). pp. 1694-1701. ISSN 0305-7453 |
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| Relation |
http://dx.doi.org/10.1093/jac/dkq186
http://iiim.csircentral.net/310/ |
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