Alvarez Francisco J, Ryman Kicki, Hooijmaijers Cornelis, Bulone Vincent, Ljungdahl Per O
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Division of Glycoscience, Royal Institute of Technology (KTH), Stockholm, Sweden.
Appl Environ Microbiol. 2015 Apr;81(8):2770-80. doi: 10.1128/AEM.03595-14. Epub 2015 Feb 6.
The pathogenic fungus Candida albicans is the leading cause of vulvovaginal candidiasis (VVC). VVC represents a major quality-of-life issue for women during their reproductive years, a stage of life where the vaginal epithelium is subject to periodic hormonally induced changes associated with menstruation and concomitant exposure to serum as well as potential intermittent contact with seminal fluid. Seminal fluid potently triggers Candida albicans to switch from yeastlike to filamentous modes of growth, a developmental response tightly linked to virulence. Conversely, vaginal fluid inhibits filamentation. Here, we used artificial formulations of seminal and vaginal fluids that faithfully mimic genuine fluids to assess the contribution of individual components within these fluids to filamentation. The high levels of albumin, amino acids, and N-acetylglucosamine in seminal fluid act synergistically as potent inducers of filamentous growth, even at atmospheric levels of CO2 and reduced temperatures (30 °C). Using a simplified in vitro model that mimics the natural introduction of seminal fluid into the vulvovaginal environment, a pulse of artificial seminal fluid (ASF) was found to exert an enduring potential to overcome the inhibitory efficacy of artificial vaginal fluid (AVF) on filamentation. These findings suggest that a transient but substantial change in the nutrient levels within the vulvovaginal environment during unprotected coitus can induce resident C. albicans cells to engage developmental programs associated with virulent growth.
致病性真菌白色念珠菌是外阴阴道念珠菌病（VVC）的主要病因。VVC是育龄期女性生活质量的一个主要问题，在这个生命阶段，阴道上皮会经历与月经相关的周期性激素诱导变化，同时接触血清以及可能间歇性接触精液。精液能有力地促使白色念珠菌从酵母样生长模式转变为丝状生长模式，这种发育反应与毒力紧密相关。相反，阴道液会抑制丝状化。在此，我们使用了能忠实地模拟真实液体的精液和阴道液人工制剂，来评估这些液体中各个成分对丝状化的作用。精液中高水平的白蛋白、氨基酸和N - 乙酰葡糖胺协同作用，即使在大气二氧化碳水平和较低温度（30°C）下，也是丝状生长的有效诱导剂。使用一个模拟精液自然进入外阴阴道环境的简化体外模型，发现一剂人工精液（ASF）具有持久的潜力，能克服人工阴道液（AVF）对丝状化的抑制作用。这些发现表明，在无保护性交过程中，外阴阴道环境中营养水平的短暂但显著变化可诱导常驻的白色念珠菌细胞启动与毒性生长相关的发育程序。
