Abstract：
Candida auris is an emerging multi-drug resistant yeast that can cause life-threatening infections. A recent report clarified the ability of C. auris to form a biofilm with enhanced drug resistance properties in the host skin\'s deep layers. The formed biofilm may initiate further bloodstream spread and immune escape. Therefore, we propose that secreted chemicals from the biofilm may facilitate fungal pathogenesis. In response to this interaction, the host skin may develop potential defensive mechanisms. Comparative transcriptomics was performed on the host dermal cells in response to indirect interaction with C. auris biofilm through Transwell inserts compared to planktonic cells. Furthermore, the effect of antifungals including caspofungin and fluconazole was studied. The obtained data showed that the dermal cells exhibited different transcriptional responses. Kyoto Encyclopedia of Genes and Genomes and Reactome analyses identified potential defensive responses employed by the dermal cells and potential toxicity induced by C. auris. Additionally, our data indicated that the dominating toxic effect was mediated by ferroptosis; which was validated by qRT-PCR, cytotoxicity assay, and flow cytometry. On the other hand, the viability of C. auris biofilm was enhanced and accompanied by upregulation of MDR1, and KRE6 upon interaction with dermal cells; both genes play significant roles in drug resistance and biofilm maturation, respectively. This study for the first-time shed light on the dominating defensive responses of human dermal cells, microbe colonization site, to C. auris biofilm and its toxic effects. Further, it demonstrates how C. auris biofilm responds to the defensive mechanisms developed by the human dermal cells.
摘要：
耳念珠菌是一种新兴的多药耐药酵母，可引起危及生命的感染。最近的报告阐明了C.auris在宿主皮肤深层形成具有增强的耐药性特性的生物膜的能力。形成的生物膜可以引发进一步的血流扩散和免疫逃逸。因此,我们认为从生物膜中分泌的化学物质可能促进真菌的发病。为了回应这种互动，宿主皮肤可能形成潜在的防御机制。与浮游细胞相比,在宿主真皮细胞上进行比较转录组学,以响应通过Transwell插入物与C.auris生物膜的间接相互作用。此外，研究了包括卡泊芬净和氟康唑在内的抗真菌药的效果。获得的数据显示真皮细胞表现出不同的转录应答。《京都基因和基因组百科全书》和Reactome分析确定了真皮细胞采用的潜在防御性反应和C.auris诱导的潜在毒性。此外,我们的数据表明，主要的毒性作用是由铁凋亡介导的；这通过qRT-PCR验证，细胞毒性试验，和流式细胞术。另一方面,与真皮细胞相互作用后，金丝酵母生物膜的活力增强，并伴随着MDR1和KRE6的上调；这两个基因在耐药性和生物膜成熟中起着重要作用，分别。这项研究首次揭示了人类真皮细胞的主要防御反应，微生物定植位点，金黄色葡萄球菌生物膜及其毒性作用。Further,它证明了C.auris生物膜如何响应人类真皮细胞开发的防御机制。
