Hypoxia and Temperature Regulated Morphogenesis in Candida albicans

Area of Science:

• Microbiology
• Molecular Biology
• Mycology

Background:

• Candida albicans is a human fungal pathogen and gut commensal.
• It adapts to low-oxygen conditions, repressing hyphal development via transcription factor Efg1.
• Efg1 activates filamentation under normal oxygen (normoxia).

Purpose of the Study:

• To investigate the regulatory mechanisms of Efg1 in Candida albicans under hypoxic conditions.
• To identify hypoxia-specific target genes regulated by Efg1 and Ace2.
• To elucidate the interconnected regulatory network controlling fungal morphogenesis.

Main Methods:

• Genome-wide binding site analysis for Efg1 under hypoxia.
• Transcriptional analyses of EFG1, ACE2, BCR1, and BRG1.
• Investigating the role of phosphorylation sites and temperature on Efg1 function.

Main Results:

• Efg1's repressive function under hypoxia is N-terminus dependent, temperature-sensitive (≤35°C), and modulated by phosphorylation.
• Identified 300 hypoxia-specific Efg1 target genes, partially overlapping with Ace2 binding sites.
• Discovered an interconnected regulatory hub (Efg1/Bcr1 negative, Ace2/Brg1 positive) controlling gene expression under hypoxia, influenced by CO2.

Conclusions:

• Candida albicans employs intricate, temperature-dependent regulatory mechanisms to control hyphal morphogenesis in hypoxic environments.
• These mechanisms restrict filamentation in oxygen-poor niches, potentially aiding persistence as a commensal.
• The Efg1-Ace2 regulatory circuit is crucial for adapting to host microenvironments.