Department of Microbiology, Institute of Experimental and Clinical Research, Laboratory of Medical Microbiology, Université Catholique De Louvain, Brussels, Belgium.
University Hospital Saint-Luc, Brussels, Belgium.
Int J Mycobacteriol. 2020 Jan-Mar;9(1):71-75. doi: 10.4103/ijmy.ijmy_181_19.
Mycobacterium abscessus is notorious for being intrinsically resistant to most antibiotics. Antibiotic efflux is one of the mechanisms used by M. abscessus to pump out antibiotics from their cells. Inhibiting efflux pumps (EPs) can be an attractive strategy to enhance the activity of drugs. The objective of this study is to determine the activity of EP inhibitors (EPIs) to enhance the efficacy of the new drug bedaquiline against M. abscessus clinical isolates.
A total of 31 phenotypically and genotypically identified M. abscessus subsp. abscessus, M. abscesss subsp. massiliense, and M. abscessus subsp. bolletii clinical isolates were studied. The contribution of EPs was determined by investigating the minimum inhibitory concentration (MIC) levels of bedaquiline reduction in the absence and presence of EPIs verapamil and reserpine using the resazurin microtiter assay.
The observed bedaquiline MIC reduction by verapamil was observed in 100% isolates and by reserpine in 54.8% isolates. Bedaquiline MIC was 4-32-fold using verapamil with M. abscessus subsp. bolletii showing the highest fold change and between 2- and 4-fold using reserpine.
The results obtained in this study confirm that bedaquiline MIC decreased in the presence of EPIs verapamil and reserpine in clinical isolates of M. abscessus. Verapamil was the most effective EPI. As shown in previous studies, verapamil may have clinical potential as adjunctive therapy to enhance the effect of bedaquiline.
脓肿分枝杆菌以对大多数抗生素固有耐药而臭名昭著。抗生素外排是脓肿分枝杆菌将抗生素从细胞中泵出的机制之一。抑制外排泵（EPs）可以成为增强药物活性的一种有吸引力的策略。本研究的目的是确定 EP 抑制剂（EPIs）对增强新药贝达喹啉对脓肿分枝杆菌临床分离株的疗效的作用。
共研究了 31 株表型和基因型鉴定的脓肿分枝杆菌亚种脓肿亚种、脓肿分枝杆菌亚种马塞亚种和脓肿分枝杆菌亚种 bolletii 临床分离株。通过使用 Resazurin 微量滴定法在不存在和存在 EPIs 维拉帕米和利血平的情况下，研究了最低抑菌浓度（MIC）水平的 bedaquiline 降低情况，从而确定了 EPs 的贡献。
维拉帕米观察到 bedaquiline MIC 降低 100%分离株，利血平观察到 54.8%分离株。维拉帕米使 bedaquiline MIC 降低 4-32 倍，脓肿分枝杆菌亚种 bolletii 显示最高的倍数变化，利血平使 bedaquiline MIC 降低 2-4 倍。
本研究的结果证实，在脓肿分枝杆菌临床分离株中，存在 EPIs 维拉帕米和利血平时，bedaquiline MIC 降低。维拉帕米是最有效的 EPI。如先前的研究所示，维拉帕米可能具有作为辅助治疗的临床潜力，以增强贝达喹啉的效果。
