Research Institute for Medical and Health Sciences, University of Sharjah, P.O. Box 27272, Sharjah, UAE.
Chemistry of Natural and Microbial Products, National Research Centre, Cairo, Egypt.
Mycopathologia. 2024 Jul 11;189(4):65. doi: 10.1007/s11046-024-00868-9.
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.
耳念珠菌是一种新兴的多药耐药酵母菌，可引起危及生命的感染。最近的一份报告阐明了耳念珠菌在宿主皮肤深层形成具有增强耐药特性的生物膜的能力。形成的生物膜可能会引发进一步的血流传播和免疫逃逸。因此，我们提出生物膜分泌的化学物质可能有助于真菌发病机制。作为对这种相互作用的反应，宿主皮肤可能会发展出潜在的防御机制。通过 Transwell 插入物对宿主真皮细胞进行了比较转录组学研究，以间接与耳念珠菌生物膜相互作用，与浮游细胞进行了比较。此外，还研究了包括卡泊芬净和氟康唑在内的抗真菌药物的作用。获得的数据表明，真皮细胞表现出不同的转录反应。京都基因与基因组百科全书和反应组分析确定了真皮细胞所采用的潜在防御反应和耳念珠菌引起的潜在毒性。此外，我们的数据表明，主导毒性作用是由铁死亡介导的；这通过 qRT-PCR、细胞毒性测定和流式细胞术进行了验证。另一方面，与真皮细胞相互作用时，耳念珠菌生物膜的活力增强，并伴随着 MDR1 和 KRE6 的上调；这两个基因分别在耐药性和生物膜成熟中起着重要作用。这项研究首次揭示了人类真皮细胞对耳念珠菌生物膜的主导防御反应，以及微生物定植部位及其毒性作用。此外，它还展示了耳念珠菌生物膜如何对人类真皮细胞开发的防御机制做出反应。
