Browsing by Author "Wang, Shuai"

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    Advances in the development of molecular genetic tools for Mycobacterium tuberculosis
    (Elsevier, 2018-07) Chiranjibi, Chhotaray; Yaoju, Tan; Mugweru, Julius; Islam, Md Mahmudul; Hameed, H.M. Adnan; Wang, Shuai; Lu, Zhili; Wang, Changwei; Li, Xinjie; Tan, Shouyong; Liu, Jianxiong; Zhang, Tianyu
    Mycobacterium tuberculosis, a Gram-positive bacterium of great clinical relevance, is a lethal pathogen owing to its complex physiological characteristics and development of drug resistance. Several molecular genetic tools have been developed in the past few decades to study this microorganism. These tools have been instrumental in understanding how M. tuberculosis became a successful pathogen. Advanced molecular genetic tools have played a significant role in exploring the complex pathways involved in M. tuberculosis pathogenesis. Here, we review various molecular genetic tools used in the study of M. tuberculosis. Further, we discuss the applications of clustered regularly interspaced short palindromic repeat interference (CRISPRi), a novel technology recently applied in M. tuberculosis research to study target gene functions. Finally, prospective outcomes of the applications of molecular techniques in the field of M. tuberculosis genetic research are also discussed.
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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.