ABSTRACT

Candida albicans-related bloodstream infections are often associated with infected central venous catheters (CVC) triggered by microbial adhesion and biofilm formation. We utilized single-cell force spectroscopy (SCFS) and flow chamber models to investigate the adhesion behavior of C. albicans yeast cells and germinated cells to naïve and human blood plasma (HBP)-coated CVC tubing. Germinated cells demonstrated up to 56.8-fold increased adhesion forces to CVC surfaces when compared to yeast cells. Coating of CVCs with HBP significantly increased the adhesion of 60-min germinated cells but not of yeast cells and 30-min germinated cells. Under flow conditions comparable to those in major human veins, germinated cells displayed a flow directional-orientated adhesion pattern to HBP-coated CVC material, suggesting the germ tip to serve as the major adhesive region. None of the above-reported phenotypes were observed with germinated cells of an als3Δ deletion mutant, which displayed similar adhesion forces to CVC surfaces as the isogenic yeast cells. Germinated cells of the als3Δ mutant also lacked a clear flow directional-orientated adhesion pattern on HBP-coated CVC material, indicating a central role for Als3 in the adhesion of germinated C. albicans cells to blood exposed CVC surfaces. In the common model of C. albicans, biofilm formation is thought to be mediated primarily by yeast cells, followed by surface-triggered the formation of hyphae. We suggest an extension of this model in which C. albicans germ tubes promote the initial adhesion to blood-exposed implanted medical devices via the germ tube-associated adhesion protein Als3.

摘要

与白色念珠菌相关的血液感染通常与微生物粘附和生物膜形成触发的感染的中心静脉导管（CVC）有关。我们利用单细胞力谱（SCFS）和流动室模型来研究白色念珠菌的粘附行为酵母细胞和发芽细胞连接到幼稚和人血浆（HBP）涂层的CVC管。与酵母细胞相比，发芽细胞对CVC表面的粘附力提高了56.8倍。用HBP包被CVC可以显着增加60分钟发芽细胞的粘附，但不能增加酵母细胞和30分钟发芽细胞的粘附。在与人类主要静脉类似的流动条件下，发芽的细胞对HBP涂层的CVC材料表现出流向定向的粘附模式，表明胚芽尖端可作为主要的粘附区域。als3Δ缺失突变体的萌发细胞未观察到上述表型，该突变体对CVC表面的粘附力与同基因酵母细胞相似。als3的发芽细胞Δ突变体在HBP涂层的CVC材料上也缺乏清晰的流向定向粘附模式，表明Als3在发芽的白色念珠菌细胞与血液暴露的CVC表面的粘附中起着核心作用。在白色念珠菌的常见模型中，生物膜的形成被认为主要是由酵母细胞介导的，其次是表面触发的菌丝的形成。我们建议该模型的扩展，其中白色念珠菌胚芽管通过胚芽相关的粘附蛋白Als3促进与血液接触的植入医疗设备的初始粘附。