KU Leuven, Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, Heverlee-Leuven, Belgium.
VIB-KU Leuven, Center for Microbiology, Flanders, Belgium.
Antimicrob Agents Chemother. 2017 Dec 21;62(1). doi: 10.1128/AAC.01767-17. Print 2018 Jan.
In this study, we investigated the potential antifungal activity of the alkylphospholipid oleylphosphocholine (OlPC), a structural analogue of miltefosine, on and biofilm formation. The effect of OlPC on and biofilms inside triple-lumen polyurethane catheters was studied. biofilms were developed subcutaneously after catheter implantation on the lower back of Sprague-Dawley rats. Animals were treated orally with OlPC (20 mg/kg of body weight/day) for 7 days. The effect of OlPC on biofilms that developed on the mucosal surface was studied in an model of oral candidiasis. The role of OlPC in morphogenesis was investigated by using hypha-inducing media, namely, Lee, Spider, and RPMI 1640 media. OlPC displayed activity against both planktonic cells and biofilms. To completely abolish preformed, 24-h-old biofilms, higher concentrations (8, 10, and 13 mg/liter) were needed. Moreover, OlPC was able to reduce biofilms formed by caspofungin-resistant clinical isolates and acted synergistically when combined with caspofungin. The daily oral administration of OlPC significantly reduced biofilms that developed subcutaneously. In addition, OlPC decreased biofilm formation on mucosal surfaces. Interestingly, the application of subinhibitory concentrations of OlPC already inhibited the yeast-to-hypha transition, a crucial virulence factor of We document, for the first time, the effects of OlPC on cells and suggest the potential use of OlPC for the treatment of biofilm-associated infections.
在这项研究中，我们研究了烷基磷脂油酰磷胆碱（OlPC）的潜在抗真菌活性，OlPC 是米替福新的结构类似物，研究其对白色念珠菌和近平滑念珠菌生物膜形成的影响。研究了 OlPC 对皮下植入三腔聚氨酯导管内白色念珠菌和近平滑念珠菌生物膜的影响。将生物膜在 Sprague-Dawley 大鼠的下背部皮下植入后形成。动物口服给予 OlPC（20mg/kg 体重/天）治疗 7 天。在口腔念珠菌病模型中研究了 OlPC 对黏膜表面生物膜形成的影响。通过使用 Lee、Spider 和 RPMI 1640 培养基等诱导菌丝形成的培养基研究了 OlPC 在菌丝形态发生中的作用。OlPC 对浮游细胞和生物膜均有活性。为了完全消除已形成的 24 小时生物膜，需要更高的浓度（8、10 和 13mg/L）。此外，OlPC 能够减少耐卡泊芬净的临床分离株形成的生物膜，并与卡泊芬净联合使用时具有协同作用。每日口服给予 OlPC 可显著减少皮下形成的生物膜。此外，OlPC 还减少了黏膜表面的生物膜形成。有趣的是，亚抑菌浓度的 OlPC 的应用已经抑制了酵母到菌丝的转变，这是白色念珠菌的一个关键毒力因子。我们首次记录了 OlPC 对白色念珠菌细胞的影响，并提出了 OlPC 治疗生物膜相关感染的潜在用途。
