A New Phenotype in Candida-Epithelial Cell Interaction Distinguishes Colonization- versus Vulvovaginal...

Area of Science:

• Mycology and Infectious Diseases
• Women's Health
• Host-Pathogen Interactions

Background:

• Vulvovaginal candidiasis (VVC) affects a majority of women, significantly impacting quality of life.
• The transition of Candida albicans from commensal to pathogenic state in VVC is not fully understood.
• Current methods cannot reliably predict if a C. albicans strain will cause VVC.

Purpose of the Study:

• To identify distinct in vitro phenotypes differentiating VVC-causing C. albicans strains from colonizing strains.
• To investigate the host-pathogen interactions at the epithelial cell level.
• To explore the role of epithelial signaling pathways in VVC pathogenesis.

Main Methods:

• Comparison of genetic profiles (MLST) and in vitro growth/filamentation of VVC and colonizing C. albicans strains.
• Assessment of fungal proliferation and cell shedding during co-culture with vaginal epithelial cells.
• Transcriptome sequencing (RNA-seq) to analyze epithelial cell signaling pathways.

Main Results:

• VVC-derived C. albicans strains showed significantly higher fungal and epithelial cell shedding compared to colonizing strains.
• No significant differences were observed in genetic profiles or basic culture behaviors.
• Differential activation of epithelial signaling pathways, including type I interferon, was identified; inhibition of this pathway increased shedding of colonizing strains.

Conclusions:

• VVC strains possess intrinsically enhanced pathogenic potential, evidenced by increased fungal shedding and epithelial cell interaction.
• The type I interferon pathway plays a role in controlling fungal shedding, with VVC strains eliciting differential responses.
• These findings may lead to in vitro assays for evaluating VVC pathogenic potential, enabling targeted antifungal treatments and potentially displacing pathogenic strains.