Browsing by Author "Tan, Yaoju"

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    Assessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent Approach
    (American Society for Microbiology, 2020-02) Liu, Yang; Tan, Yaoju; Islam, Mahmudul M.; Cao, Yuanyuan; Lu, Xiaoyun; Zeng, Sheng; Hameed, H. M. Adnan; Zhou, Peipei; Cai, Xingshan; Wang, Shuai; Mugweru, Julius N.; Zhang, Guoliang; Yin, Huancai; Liu, Jianxiong; Nuermberger, Eric; Zhang, Tianyu
    Mycobacterium abscessus is intrinsically resistant to most antimicrobial agents. The emerging infections caused by M. abscessus and the lack of effective treatment call for rapid attention. Here, we intended to construct a selectable marker-free autoluminescent M. abscessus strain (designated UAlMab) as a real-time reporter strain to facilitate the discovery of effective drugs and regimens for treating M. abscessus. The UAlMab strain was constructed using the dif/Xer recombinase system. In vitro and in vivo activities of several drugs, including clofazimine and TB47, a recently reported cytochrome bc1 inhibitor, were assessed using UAlMab. Furthermore, the efficacy of multiple drug combinations, including the clofazimine and TB47 combination, were tested against 20 clinical M. abscessus isolates. The UAlMab strain enabled us to evaluate drug efficacy both in vitro and in live BALB/c mice in a real-time, noninvasive fashion. Importantly, although TB47 showed marginal activity either alone or in combination with clarithromycin, amikacin, or roxithromycin, the drug markedly potentiated the activity of clofazimine, both in vitro and in vivo. This study demonstrates that the use of the UAlMab strain can significantly facilitate rapid evaluation of new drugs and regimens. The clofazimine and TB47 combination is effective against M. abscessus, and dual/triple electron transport chain (ETC) targeting can be an effective therapeutic approach for treating mycobacterial infections.
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    Mutation EthAW21R confers co-resistance to prothionamide and ethionamide in both Mycobacterium bovis BCG and Mycobacterium tuberculosis H37Rv
    (Dove Press, 2018-06) Mugweru, Julius; Liu, Jianxiong; Makafe, Gaelle; Chiwala, Gift; Wang, Bangxing; Wang, Changwei; Li, Xinjie; Tan, Yaoju; Yew, Wing Wai; Tan, Shouyong; Zhang, Tianyu
    Ethionamide (ETA) and prothionamide (PRO) are interchangeably used in tuberculosis (TB) chemotherapy regimens. Subtle discrepancies between biochemical and genetic information on the modes of sensitivity and resistance of isoniazid (INH) and ETA warrants further studies. We report a new mutation – EthAW21R – in Mycobacterium bovis Bacillus Calmette-Guérin that corresponds with co-resistance to both PRO and ETA, which to the best of our knowledge has not been reported before. Our findings suggest that mutation EthAW21R could be used as a marker site for testing PRO and ETA cross-resistance