Antimicrobial and Antibiofilm Effects of Bithionol against Mycobacterium abscessus

Author:

Cao Dan1,Yuan Xin1,Jiang Xiuzhi1,Wu Tiantian1,Xiang Yanghui1,Ji Zhongkang1,Liu Jiaying1,Dong Xu1,Bi Kefan1,Tønjum Tone2ORCID,Xu Kaijin1,Zhang Ying13ORCID

Affiliation:

1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China

2. Department of Microbiology, University of Oslo, Oslo University Hospital, 0424 Oslo, Norway

3. Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China

Abstract

Mycobacterium abscessus (M. abscessus) is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs and the formation of biofilm make its clinical treatment very difficult. The FDA-approved drug library containing 3048 marketed and pharmacopeial drugs or compounds was screened at 20 μM against M. abscessus type strain 19977 in 7H9 medium, and 62 hits with potential antimicrobial activity against M. abscessus were identified. Among them, bithionol, a clinically approved antiparasitic agent, showed excellent antibacterial activity and inhibited the growth of three different subtypes of M. abscessus from 0.625 μM to 2.5 μM. We confirmed the bactericidal activity of bithionol by the MBC/MIC ratio being ≤4 and the time–kill curve study and also electron microscopy study. Interestingly, it was found that at 128 μg/mL, bithionol could completely eliminate biofilms after 48h, demonstrating an outstanding antibiofilm capability compared to commonly used antibiotics. Additionally, bithionol could eliminate 99.9% of biofilm bacteria at 64 μg/mL, 99% at 32 μg/mL, and 90% at 16 μg/mL. Therefore, bithionol may be a potential candidate for the treatment of M. abscessus infections due to its significant antimicrobial and antibiofilm activities.

Funder

National Infectious Disease Medical Center

Jinan Microecological Biomedicine Shandong Laboratory project

Research Council of Norway Reversing antimicrobial resistance

Publisher

MDPI AG

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