Ume6-dependent pathways of morphogenesis and biofilm formation in Candida auris.

Details

Serval ID
serval:BIB_21541699EAF6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ume6-dependent pathways of morphogenesis and biofilm formation in Candida auris.
Journal
Microbiology spectrum
Author(s)
Louvet M., Li J., Brandalise D., Bachmann D., Sala de Oyanguren F., Labes D., Jacquier N., Genoud C., Mucciolo A., Coste A.T., Sanglard D., Lamoth F.
ISSN
2165-0497 (Electronic)
ISSN-L
2165-0497
Publication state
Published
Issued date
19/09/2024
Peer-reviewed
Oui
Pages
e0153124
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Candida auris 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 Candida spp., C. auris 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 C. auris morphogenesis. Genetic hyperactivation of Ume6 induced filamentation and aggregation. The Ume6-hyperactivated strain (UME6 <sup>HA</sup> ) also exhibited increased adhesion to inert surface and formed biofilms of higher biomass compared to the parental strain. Transcriptomic analyses of UME6 <sup>HA</sup> 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 C. auris-specific adhesin Scf1, and the hypha-specific G1 cyclin-related protein Hgc1. The deletion of these genes in the UME6 <sup>HA</sup> 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 C. auris morphogenesis via distinct modulators.IMPORTANCEC. auris represents a public health threat because of its ability to cause difficult-to-treat infections and hospital outbreaks. The morphogenetic plasticity of C. auris, 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 C. auris. A better understanding of the mechanisms of C. auris morphogenesis may help identify novel antifungal targets.
Keywords
adhesin, aggregation, biofilm, pseudohyphae, transcriptomic
Pubmed
Open Access
Yes
Create date
24/09/2024 9:59
Last modification date
25/09/2024 7:20
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