PDF(Pubmed)
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.
摘要：
脓肿分枝杆菌(M.脓肿）是一种耐多药的非结核分枝杆菌（NTM），可引起人类广泛的感染。缺乏有效的杀菌药物和生物膜的形成使其临床治疗非常困难。含有3048种上市和药典药物或化合物的FDA批准的药物库在7H9培养基中以20μM针对脓肿分枝杆菌型菌株19977进行筛选，并鉴定了62个对脓肿分枝杆菌具有潜在抗菌活性的命中。其中,双硫酚，临床批准的抗寄生虫药,表现出优异的抗菌活性，并从0.625μM到2.5μM抑制了三种不同亚型的脓肿分枝杆菌的生长。我们通过MBC/MIC比≤4，时间杀死曲线研究和电子显微镜研究证实了联硫酚的杀菌活性。有趣的是,发现在128μg/mL时，联硫酚可以在48h后完全消除生物膜，与常用抗生素相比，具有出色的抗生物膜能力。此外,双硫酚在64μg/mL时可以消除99.9%的生物膜细菌，在32μg/mL时为99%，和90%在16μg/mL。因此,由于具有显着的抗菌和抗生物膜活性，联硫酚可能是治疗脓肿分枝杆菌感染的潜在候选者。
