对感染了白色念珠菌的人类真皮细胞进行转录组分析,发现了独特的发病机制/防御机制,尤其是铁突变。

IF 3.6 3区 生物学 Q2 MYCOLOGY Mycopathologia Pub Date : 2024-07-11 DOI:10.1007/s11046-024-00868-9
Bahgat Fayed, Sarra B Shakartalla, Hassan Sabbah, Hala Dalle, Mohamed Tannira, Abiola Senok, Sameh S M Soliman
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引用次数: 0

摘要

白色念珠菌是一种新出现的具有多重耐药性的酵母菌,可导致危及生命的感染。最近的一份报告明确指出,白色念珠菌能够在宿主皮肤深层形成具有增强耐药特性的生物膜。形成的生物膜可能会引发进一步的血液传播和免疫逃逸。因此,我们认为生物膜分泌的化学物质可能会促进真菌的致病作用。为了应对这种相互作用,宿主皮肤可能会发展出潜在的防御机制。与浮游细胞相比,我们通过 Transwell 插片对宿主皮肤细胞与 C. auris 生物膜间接相互作用的反应进行了比较转录组学研究。此外,还研究了抗真菌药物(包括卡泊芬净和氟康唑)的效果。所得数据显示,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 Reactome 分析确定了真皮细胞的潜在防御反应和 C. auris 诱发的潜在毒性。此外,我们的数据表明,主要的毒性效应是由铁突变介导的;这一点已通过 qRT-PCR、细胞毒性测定和流式细胞术得到验证。另一方面,C. auris 生物膜的活力增强,并伴随着与皮肤细胞相互作用时 MDR1 和 KRE6 的上调;这两个基因分别在耐药性和生物膜成熟过程中发挥重要作用。这项研究首次揭示了作为微生物定殖场所的人体真皮细胞对 C. auris 生物膜的主要防御反应及其毒性作用。此外,它还展示了 C. auris 生物膜如何对人类真皮细胞建立的防御机制做出反应。
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Transcriptome Analysis of Human Dermal Cells Infected with Candida auris Identified Unique Pathogenesis/Defensive Mechanisms Particularly Ferroptosis.

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.

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来源期刊
Mycopathologia
Mycopathologia 生物-真菌学
CiteScore
6.80
自引率
3.60%
发文量
76
审稿时长
3 months
期刊介绍: Mycopathologia is an official journal of the International Union of Microbiological Societies (IUMS). Mycopathologia was founded in 1938 with the mission to ‘diffuse the understanding of fungal diseases in man and animals among mycologists’. Many of the milestones discoveries in the field of medical mycology have been communicated through the pages of this journal. Mycopathologia covers a diverse, interdisciplinary range of topics that is unique in breadth and depth. The journal publishes peer-reviewed, original articles highlighting important developments concerning medically important fungi and fungal diseases. The journal highlights important developments in fungal systematics and taxonomy, laboratory diagnosis of fungal infections, antifungal drugs, clinical presentation and treatment, and epidemiology of fungal diseases globally. Timely opinion articles, mini-reviews, and other communications are usually invited at the discretion of the editorial board. Unique case reports highlighting unprecedented progress in the diagnosis and treatment of fungal infections, are published in every issue of the journal. MycopathologiaIMAGE is another regular feature for a brief clinical report of potential interest to a mixed audience of physicians and laboratory scientists. MycopathologiaGENOME is designed for the rapid publication of new genomes of human and animal pathogenic fungi using a checklist-based, standardized format.
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