Candida auris is an enigmatic yeast that provides substantial global risk in health care facilities and intensive care units. A unique phenotype exhibited by certain isolates of C. auris is their ability to form small clusters of cells known as aggregates, which have been to a limited extent described in the context of pathogenic traits. In this study, we screened several nonaggregative and aggregative C. auris isolates for biofilm formation, where we observed a level of heterogeneity among the different phenotypes. Next, we utilized an RNA sequencing approach to investigate the transcriptional responses during biofilm formation of a nonaggregative and aggregative isolate of the initial pool. Observations from these analyses indicate unique transcriptional profiles in the two isolates, with several genes identified relating to proteins involved in adhesion and invasion of the host in other fungal species. From these findings, we investigated for the first time the fungal recognition and inflammatory responses of a three-dimensional skin epithelial model to these isolates. In these models, a wound was induced to mimic a portal of entry for C. auris. We show that both phenotypes elicited minimal response in the model minus induction of the wound, yet in the wounded tissue, both phenotypes induced a greater response, with the aggregative isolate more proinflammatory. This capacity of aggregative C. auris biofilms to generate such responses in the wounded skin highlights how this opportunistic yeast is a high risk within the intensive care environment where susceptible patients have multiple indwelling lines.

中文翻译：

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假丝酵母表型异质性决定了体外致病性。

黄金假丝酵母是一种神秘的酵母，会给医疗机构和重症监护病房带来巨大的全球风险。通过某些分离物表现出独特的表型C.耳是它们形成被称为聚集体细胞，其已在致病性状的上下文中描述在有限范围内的小群的能力。在这项研究中，我们筛选了几种非聚合和非聚合梭菌分离生物膜形成，我们观察到了不同表型之间的异质性水平。接下来，我们利用RNA测序方法来研究初始池的非聚集和聚集分离物在生物膜形成过程中的转录反应。从这些分析中观察到的结果表明，两种分离物中的转录谱具有独特性，其中一些基因与参与宿主在其他真菌物种中的粘附和侵袭的蛋白质有关。从这些发现，我们首次研究了三维皮肤上皮模型对这些分离株的真菌识别和炎症反应。在这些模型中，诱导伤口模拟金黄色葡萄球菌的进入门。我们显示这两种表型在减去伤口诱导的模型中均引起最小的反应，但在受伤的组织中，两种表型均诱导出更大的反应，而聚合分离物则更具促炎性。在受伤的皮肤中聚集的梭状芽胞杆菌生物膜产生这种反应的能力凸显了这种机会性酵母在重症监护环境中的高风险，在重症监护环境中，易感患者有多个留置系。