A CO₂ sensing module modulates β-1,3-glucan exposure in Candida albicans

Area of Science:

• Medical Mycology
• Immunology
• Molecular Biology

Background:

• Commensal fungi like Candida albicans evade host immunity using strategies such as masking pathogen-associated molecular patterns (PAMPs).
• C. albicans reduces exposure of β-1,3-glucan, a proinflammatory PAMP, in response to host signals like lactate and hypoxia.
• Clinical isolates of C. albicans exhibit variability in their β-1,3-glucan masking response.

Purpose of the Study:

• To investigate the genetic basis of phenotypic variability in C. albicans' β-1,3-glucan masking response.
• To identify novel regulatory pathways controlling PAMP exposure in C. albicans.
• To understand the role of the Nce103-related signaling module in immune evasion.

Main Methods:

• Comparative RNA sequencing of responsive and non-responsive C. albicans clinical isolates.
• Gene deletion studies to assess the function of candidate genes (PHO84, NCE103).
• Analysis of the Sch9-Rca1-Nce103 signaling module's role in β-1,3-glucan exposure.

Main Results:

• Phenotypic variability in β-1,3-glucan masking was observed among clinical isolates.
• Deletion of PHO84 and NCE103 attenuated β-1,3-glucan masking.
• The Sch9-Rca1-Nce103 signaling module was identified as a key regulator of β-1,3-glucan exposure in response to hypoxia and lactate.

Conclusions:

• A novel regulatory module (Sch9-Rca1-Nce103) controls PAMP exposure in C. albicans.
• This module is crucial for C. albicans' immune evasion strategies under host-specific conditions.
• The findings provide insights into fungal pathogenesis and host-pathogen interactions.