Chen Suting, Teng Tianlu, Zhang Zhuman, Shang Yuanyuan, Xiao Hua, Jiang Guanglu, Wang Fen, Jia Junnan, Dong Lingling, Zhao Liping, Chu Naihui, Huang Hairong
National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People's Republic of China.
Department of Tuberculosis; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People's Republic of China.
Infect Drug Resist. 2021 Mar 23;14:1199-1208. doi: 10.2147/IDR.S303113. eCollection 2021.
Treatment choices for () infections are very limited, and the prognosis is generally poor. Effective new antibiotics or repurposing existing antibiotics against infection are urgently needed. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a member of the lipophilic weak acid class, is known as an efflux pump inhibitor for . The aim of this study was to determine the inhibitory activity of CCCP as a potential novel antibiotic against .
A total of 47 reference strains of different mycobacterial species and 60 clinical isolates of were enrolled. In vitro inhibitory activity of CCCP was accessed using microplates alamar blue method with the reference and clinical isolates. The activity of CCCP against intracellular residing within macrophage was also evaluated by intracellular colony numerating assay.
CCCP exhibited good activity against clinical isolates in vitro, the minimum inhibitory concentration (MIC) ranged from 0.47 μg/mL to 3.75 μg/mL, with a MIC of 1.875 μg/mL and MIC of 3.75 μg/mL. At concentrations safe for the cells, CCCP exhibited highly intracellular bactericidal activities against and reference strains, with inhibitory rates of 84.8%±8.8% and 72.5%±13.7%, respectively. CCCP demonstrated bactericidal activity against intracellular that was comparable to clarithromycin, and concentration-dependent antimicrobial activity against in macrophages was observed. In addition, CCCP also exhibited good activities against most reference strains of rapidly growing mycobacterial species.
CCCP could be a potential candidate of novel antimicrobiological agent to treat infection.
()感染的治疗选择非常有限,且预后通常较差。迫切需要有效的新型抗生素或重新利用现有抗生素来治疗该感染。羰基氰3-氯苯腙(CCCP),属于亲脂性弱酸类,是已知的()外排泵抑制剂。本研究的目的是确定CCCP作为一种潜在新型抗生素对()的抑制活性。
共纳入47株不同分枝杆菌属的参考菌株和60株()临床分离株。使用微孔板阿拉玛蓝法对参考菌株和临床分离株评估CCCP的体外抑制活性。还通过细胞内菌落计数试验评估CCCP对巨噬细胞内()的活性。
CCCP在体外对()临床分离株表现出良好活性,最低抑菌浓度(MIC)范围为0.47μg/mL至3.75μg/mL,MIC50为1.875μg/mL,MIC90为3.75μg/mL。在对细胞安全的浓度下,CCCP对()和()参考菌株表现出高度的细胞内杀菌活性,抑制率分别为84.8%±8.8%和72.5%±13.7%。CCCP对细胞内()的杀菌活性与克拉霉素相当,且在巨噬细胞中观察到对()的浓度依赖性抗菌活性。此外,CCCP对大多数快速生长分枝杆菌属参考菌株也表现出良好活性。
CCCP可能是治疗()感染的新型抗微生物剂的潜在候选药物。