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外排泵抑制控制 种复合体的生长并增强抗真菌敏感性。

Efflux pump inhibition controls growth and enhances antifungal susceptibility of species complex.

机构信息

Department of Pathology and Legal Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.

Post Graduate Program in Veterinary Sciences, College of Veterinary Medicine, State University of Ceará, Fortaleza, Ceará, Brazil.

出版信息

Future Microbiol. 2020 Jan;15:9-20. doi: 10.2217/fmb-2019-0186. Epub 2020 Feb 11.

Abstract

To evaluate the inhibition of efflux pumps by using promethazine (PMZ) as a strategy to control species complex (FSSC). The susceptibility of FSSC strains to PMZ and the interaction between PMZ and antifungals were evaluated. The efflux pump activity was confirmed by flow cytometry with rhodamine 6G. Finally, PMZ was tested against FSSC biofilms. PMZ inhibited FSSC planktonic growth and showed synergism with antifungals. PMZ reduced R6G efflux and inhibited cell adhesion, impaired the development of biofilms and disrupted mature biofilms. PMZ-challenged biofilms showed increased sensitivity to amphotericin B. The study provides indirect evidence of the occurrence of efflux pumps in FSSC and opens a perspective for this target in the control of fusariosis.

摘要

为评估通过使用吩噻嗪(PMZ)抑制外排泵来控制镰孢菌物种复合体(FSSC),评估了 FSSC 菌株对 PMZ 的敏感性以及 PMZ 与抗真菌药物之间的相互作用。用罗丹明 6G 通过流式细胞术证实了外排泵的活性。最后,测试了 PMZ 对 FSSC 生物膜的作用。PMZ 抑制 FSSC 浮游生长,并与抗真菌药物表现出协同作用。PMZ 减少了 R6G 的外排并抑制了细胞黏附,破坏了生物膜的形成并破坏了成熟的生物膜。受到 PMZ 挑战的生物膜对两性霉素 B 的敏感性增加。该研究为 FSSC 中外排泵的发生提供了间接证据,并为该靶标在控制镰孢菌病方面开辟了新的视角。

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