Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Flow Cytometry Facility, University of Lausanne, Lausanne, Switzerland.
Microbiol Spectr. 2024 Nov 5;12(11):e0153124. doi: 10.1128/spectrum.01531-24. Epub 2024 Sep 19.
is a yeast pathogen causing nosocomial outbreaks of candidemia. Its ability to adhere to inert surfaces and to be transmitted from one patient to another via medical devices is of particular concern. Like other spp., has the ability to transition from the yeast form to pseudohyphae and to build biofilms. Moreover, some isolates have a unique capacity to form aggregates. These morphogenetic changes may impact virulence. In this study, we demonstrated the role of the transcription factor Ume6 in morphogenesis. Genetic hyperactivation of Ume6 induced filamentation and aggregation. The Ume6-hyperactivated strain () also exhibited increased adhesion to inert surface and formed biofilms of higher biomass compared to the parental strain. Transcriptomic analyses of revealed enrichment of genes encoding for adhesins, proteins involved in cell wall organization, sterol biosynthesis, and aspartic protease activities. The three most upregulated genes compared to wild-type were those encoding for the agglutin-like sequence adhesin Als4498, the -specific adhesin Scf1, and the hypha-specific G1 cyclin-related protein Hgc1. The deletion of these genes in the background showed that Ume6 controls filamentation via Hgc1 and aggregation via Als4498 and Scf1. Adhesion to inert surface was essentially triggered by Scf1. However, Als4498 and Hgc1 were also crucial for biofilm formation. Our data show that Ume6 is a universal regulator of morphogenesis via distinct modulators.IMPORTANCE represents a public health threat because of its ability to cause difficult-to-treat infections and hospital outbreaks. The morphogenetic plasticity of , including its ability to filament, to form aggregates or biofilms on inert surfaces, is important to the fungus for interhuman transmission, skin or catheter colonization, tissue invasion, antifungal resistance, and escape of the host immune system. This work deciphered the importance of Ume6 in the control of distinct pathways involved in filamentation, aggregation, adhesion, and biofilm formation of . A better understanding of the mechanisms of morphogenesis may help identify novel antifungal targets.
是一种酵母病原体,可引起医院内念珠菌血症的暴发。它具有黏附于惰性表面并通过医疗设备从一个患者传播到另一个患者的能力,这尤其令人担忧。与其他 spp. 一样, 具有从酵母形式转变为假菌丝和形成生物膜的能力。此外,一些分离株具有独特的形成聚集体的能力。这些形态发生变化可能会影响毒力。在这项研究中,我们证明了转录因子 Ume6 在 形态发生中的作用。Ume6 的遗传超激活诱导了菌丝和聚集。与亲本菌株相比,Ume6 超激活菌株 () 也表现出对惰性表面的粘附增加,并形成了更高生物量的生物膜。与野生型相比, 转录组分析显示编码粘附素、参与细胞壁组织、固醇生物合成和天冬氨酸蛋白酶活性的蛋白质的基因富集。与野生型相比,上调最明显的三个基因是编码凝集素样序列粘附素 Als4498、 -特异性粘附素 Scf1 和菌丝特异性 G1 周期蛋白相关蛋白 Hgc1 的基因。在 背景下缺失这些基因表明,Ume6 通过 Hgc1 控制菌丝形成,通过 Als4498 和 Scf1 控制聚集。对惰性表面的粘附主要由 Scf1 触发。然而,Als4498 和 Hgc1 对于生物膜形成也至关重要。我们的数据表明,Ume6 通过不同的调节剂成为 形态发生的通用调节剂。重要的是,由于其引起难以治疗的感染和医院暴发的能力,它对公共卫生构成威胁。 的形态可塑性,包括其在惰性表面上丝状形成、形成聚集体或生物膜的能力,对于真菌在人与人之间的传播、皮肤或导管定植、组织侵袭、抗真菌耐药性和逃避宿主免疫系统的能力非常重要。这项工作阐明了 Ume6 在控制丝状形成、聚集、粘附和生物膜形成的不同途径中的重要性。更好地了解 的形态发生机制可能有助于确定新的抗真菌靶点。