Assessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent Approach

Liu, Yang1; Tan, Yaoju2; Islam, M. Mahmudul1,3; Cao, Yuanyuan1; Lu, Xiaoyun4; Zeng, Sheng1; Hameed, H. M. Adnan1,3; Zhou, Peipei1; Cai, Xingshan2; Wang, Shuai1,3; Mugweru, Julius N.1,3,5; Zhang, Guoliang6; Yin, Huancai7; Liu, Jianxiong2; Nuermberger, Eric8; Zhang, Tianyu1,3

2020-03

10.1128/AAC.01881-19

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   影响因子和分区

0066-4804

1098-6596

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 bc(1) 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.

Mycobacterium abscessus cytochrome bc(1) inhibitor TB47 clofazimine autoluminescent

SCI

英语

其他

Guangdong Province grant[2016TX03R095]

Microbiology ; Pharmacology & Pharmacy

Microbiology ; Pharmacology & Pharmacy

WOS:000516763200037

AMER SOC MICROBIOLOGY

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, Guangzhou, Peoples R China
2.Guangzhou Chest Hosp, Dept Clin Lab, State Key Lab Resp Dis, Guangzhou, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Jinan Univ, Sch Pharm, Guangzhou, Peoples R China
5.Univ Embu, Dept Biol Sci, Embu, Kenya
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Guangdong Key Lab Emerging Infect Dis, Shenzhen, Peoples R China
7.Chinese Acad Sci, Key Lab Biomed Diagnost, Suzhou Inst Biomed Engn & Technol, Suzhou, Jiangsu, Peoples R China
8.Johns Hopkins Univ, Dept Med, Ctr TB Res, Baltimore, MD USA

Liu, Yang,Tan, Yaoju,Islam, M. Mahmudul,et al. Assessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent Approach[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2020,64(3).

Liu, Yang.,Tan, Yaoju.,Islam, M. Mahmudul.,Cao, Yuanyuan.,Lu, Xiaoyun.,...&Zhang, Tianyu.(2020).Assessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent Approach.ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,64(3).

Liu, Yang,et al."Assessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent Approach".ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 64.3(2020).