Carbonyl Cyanide 3-Chlorophenylhydrazone (CCCP) Exhibits Direct Antibacterial Activity Against Mycobacterium abscessus

羰基氰化物 3-氯苯腙 (CCCP) 对脓肿分枝杆菌具有直接抗菌活性

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作者:Suting Chen #, Tianlu Teng #, Zhuman Zhang, Yuanyuan Shang, Hua Xiao, Guanglu Jiang, Fen Wang, Junnan Jia, Lingling Dong, Liping Zhao, Naihui Chu, Hairong Huang

Conclusion

CCCP could be a potential candidate of novel antimicrobiological agent to treat M. abscessus infection.

Methods

A total of 47 reference strains of different mycobacterial species and 60 clinical isolates of M. abscessus 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 M. abscessus residing within macrophage was also evaluated by intracellular colony numerating assay.

Objective

Treatment choices for Mycobacterium abscessus (M. abscessus) infections are very limited, and the prognosis is generally poor. Effective new antibiotics or repurposing existing antibiotics against M. abscessus 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 Mycobacterium tuberculosis. The aim of this study was to determine the inhibitory activity of CCCP as a potential novel antibiotic against M. abscessus.

Results

CCCP exhibited good activity against M. abscessus clinical isolates in vitro, the minimum inhibitory concentration (MIC) ranged from 0.47 μg/mL to 3.75 μg/mL, with a MIC50 of 1.875 μg/mL and MIC90 of 3.75 μg/mL. At concentrations safe for the cells, CCCP exhibited highly intracellular bactericidal activities against M. abscessus and M. massiliense reference strains, with inhibitory rates of 84.8%±8.8% and 72.5%±13.7%, respectively. CCCP demonstrated bactericidal activity against intracellular M. abscessus that was comparable to clarithromycin, and concentration-dependent antimicrobial activity against M. abscessus in macrophages was observed. In addition, CCCP also exhibited good activities against most reference strains of rapidly growing mycobacterial species.

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