Establishment and application of the screening model of the Mycobacterium tuberculosis β-lactamase BlaC inhibitors

doi:10.5246/jcps.2016.03.022

Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (3): 189-195.DOI: 10.5246/jcps.2016.03.022

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Establishment and application of the screening model of the Mycobacterium tuberculosis β-lactamase BlaC inhibitors

Yishuang Liu¹, Jiayin Zheng², Shuchao Huang¹, Yan Guan¹, Chunling Xiao^1*

1. National Key Laboratory for Screening New Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
2. Department of Neurobiology, Capital Medical University, Beijing 100069, China

Received:2016-01-18 Revised:2016-02-17 Online:2016-03-29 Published:2016-02-24
Contact: Tel.: 861063020226, E-mail: xiaocl318@163.com
Supported by:
Fundamental Research Funds for Central Public Welfare Research Institutes (Grant No. 2015PT350001) and National Major Scientific and Technological Special Project for “Significant New Drugs Development” (Grant No. 2015ZX09102007-009).

Abstract

Abstract:

With the continuous emergence and rapid spread of multidrug-resistant and extensively-drug-resistant Mycobacterium tuberculosis strains, it is imperative to develop novel therapies against this bacterium. The intrinsic β-lactam resistance ofM. tuberculosis is primarily due to the production of an Ambler class-A β-lactamase BlaC, which limits the application of β-lactam antibiotics in the treatment of tuberculosis. Therefore, the inhibitors of BlaC could be novel anti-tuberculosis drug synergistic agents to recover the sensibility of M. Tuberculosis to the β-lactam antibiotics. In the present study, BlaC of M. tuberculosis was expressed and purified to establish a screening model of the BlaC inhibitors. The screening conditions were determined, and the screening model was evaluated to fit for the high throughput screening. A total of 22 BlaC inhibitors were screened out from 26 400 compound samples with a positive rate of 0.083%. Taken together, our findings lay the foundation for the discovery of novel anti-tuberculosis drug synergistic agents in clinic.

Key words: Mycobacterium tuberculosis, β-Lactamase, BlaC, High-through screening model, Anti-tuberculosis drug synergistic agents

CLC Number:

R965

Supporting:

Yishuang Liu, Jiayin Zheng, Shuchao Huang, Yan Guan, Chunling Xiao. Establishment and application of the screening model of the Mycobacterium tuberculosis β-lactamase BlaC inhibitors[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(3): 189-195.

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Establishment and application of the screening model of the Mycobacterium tuberculosis β-lactamase BlaC inhibitors

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