Ifu5, a WW domain-containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans.
Biofilm
Efg1
WW domain
cell wall integrity
hyphal morphogenesis
hypoxia
Journal
Cellular microbiology
ISSN: 1462-5822
Titre abrégé: Cell Microbiol
Pays: India
ID NLM: 100883691
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
11
07
2019
revised:
03
10
2019
accepted:
23
10
2019
pubmed:
19
11
2019
medline:
23
3
2021
entrez:
19
11
2019
Statut:
ppublish
Résumé
Hypoxic adaptation pathways, essential for Candida albicans pathogenesis, are tied to its transition from a commensal to a pathogen. Herein, we identify a WW domain-containing protein, Ifu5, as a determinant of hypoxic adaptation that also impacts normoxic responses in this fungus. Ifu5 activity supports glycosylation homeostasis via the Cek1 mitogen-activated protein kinase-dependent up-regulation of PMT1, under normoxia. Transcriptome analysis of ifu5Δ/Δ under normoxia shows a significant up-regulation of the hypoxic regulator EFG1 and EFG1-dependent genes. We demonstrate physical interaction between Ifu5 by virtue of its WW domain and Efg1 that represses EFG1 expression under normoxia. This interaction is lost under hypoxic growth conditions, relieving EFG1 repression. Hypoxic adaptation processes such as filamentation and biofilm formation are affected in ifu5Δ/Δ cells revealing the role of Ifu5 in hypoxic signalling and modulating pathogenicity traits of C. albicans under varied oxygen conditions. Additionally, the WW domain of Ifu5 facilitates its role in hypoxic adaptation, revealing the importance of this domain in providing a platform to integrate various cellular processes. These data forge a relationship between Efg1 and Ifu5 that fosters the role of Ifu5 in hypoxic adaptation thus illuminating novel strategies to undermine the growth of C. albicans.
Identifiants
pubmed: 31736226
doi: 10.1111/cmi.13140
pmc: PMC7614792
mid: EMS178618
doi:
Substances chimiques
DNA-Binding Proteins
0
EFG1 protein, Candida albicans
0
Fungal Proteins
0
Transcription Factors
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13140Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 101873
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N006364/1
Pays : United Kingdom
Informations de copyright
© 2019 John Wiley & Sons Ltd.
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