Ifu5, a WW domain-containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans

Sumit K. Rastogi, Lasse van Wijlick, Shivani Ror, Keunsook K. Lee, Elvira Román, Pranjali Agarwal, Nikhat Manzoor, Neil A.R. Gow, Jesús Pla, Joachim F. Ernst, Sneh L. Panwar*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere13140
Number of pages15
JournalCellular Microbiology
Volume22
Issue number2
Early online date17 Nov 2019
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Biofilm
  • cell wall integrity
  • Efg1
  • hyphal morphogenesis
  • hypoxia
  • WW domain

Fingerprint Dive into the research topics of 'Ifu5, a WW domain-containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans'. Together they form a unique fingerprint.

Cite this