Antifungal chemical compounds identified using a C. elegans pathogenicity assay.

Area of Science:

• Microbiology
• Infectious Diseases
• Drug Discovery

Background:

• Antifungal drug discovery faces challenges, necessitating innovative screening models.
• Candida albicans infections pose a significant threat, requiring new therapeutic strategies.
• Current in vitro antifungal screens may miss compounds targeting virulence factors.

Purpose of the Study:

• To develop and validate a high-throughput in vivo screening assay for antifungal compounds using a nematode model.
• To identify novel chemical compounds with antifungal activity against Candida species.
• To investigate the role of Candida pathogenesis in a whole-animal model.

Main Methods:

• Utilized Caenorhabditis elegans (C. elegans) as a model organism for Candida albicans infection.
• Developed a 96-well plate-based liquid assay for high-throughput screening of chemical libraries.
• Screened 1,266 compounds with known pharmaceutical activities for their ability to prolong nematode survival and inhibit fungal filamentation.

Main Results:

• The C. elegans assay successfully modeled lethal Candida infections, including key virulence factors like filamentation.
• Fifteen compounds (1.2%) demonstrated efficacy in prolonging nematode survival and inhibiting in vivo filamentation.
• Two identified compounds, caffeic acid phenethyl ester and enoxacin, showed antifungal activity in a murine model of candidiasis.

Conclusions:

• The C. elegans whole-animal assay is a powerful tool for identifying novel antifungal agents and studying Candida pathogenesis.
• This in vivo model can uncover compounds missed by traditional in vitro screens, potentially targeting virulence rather than growth.
• Identified compounds may serve as probes for further research and possess broader antifungal potential.