Breaking Barriers: Candidalysin Disrupts Epithelial Integrity and Induces Inflammation in a Gut-on-Chip Model

Area of Science:

• Microbiology
• Pathogenesis
• Toxicology

Background:

• Candida albicans is an opportunistic pathogen causing systemic infections.
• Candidalysin, a toxin secreted by C. albicans, breaches epithelial barriers.
• The precise impact of candidalysin on epithelial responses requires further characterization.

Purpose of the Study:

• To characterize epithelial responses to candidalysin.
• To develop scalable, quantitative methods for assessing candidalysin's toxicological effects.
• To utilize gut-on-chip models for studying candidalysin-induced damage.

Main Methods:

• Exposure of Caco-2 tubules to candidalysin on the OrganoPlate® platform.
• Evaluation of barrier integrity using trans-epithelial electrical resistance (TEER).
• Assessment of cellular damage and immune response via protein detection (LDH, cytokines, LL37) and immunostaining.

Main Results:

• Candidalysin impaired epithelial barrier integrity and increased cell permeability.
• Actin remodeling and cellular damage were observed.
• Release of LDH, cytokines, and LL37 indicated inflammation and antimicrobial activity.

Conclusions:

• Candidalysin plays a significant role in C. albicans pathogenesis by damaging epithelial barriers.
• Gut-on-chip models provide a robust platform for studying candidalysin's effects.
• Targeting candidalysin offers potential therapeutic strategies against C. albicans infections.