Biofilm Formation ofCandida albicansFacilitates Fungal Infiltration and Persister Cell Formation in Vaginal Candidiasis

Background Vaginal candidiasis is an important medical condition awaiting more effective treatment. HowCandida albicanscauses this disease and survives antifungal treatment is not yet fully understood. This study aimed to establish a comprehensive understanding of biofilm-related defensive strategies thatC. albicansuses to establish vaginal candidiasis and to survive antifungal treatment. Methods A mouse model of vaginal candidiasis was adopted to examine the formation of biotic biofilms on the vaginal epithelium and fungal infiltration by laboratory and clinical strains ofC. albicans. Histopathological changes and local inflammation in the vaginal epithelium caused byC. albicansof different biofilm phenotypes were compared. Antifungal susceptibility testing was carried out forC. albicansgrown as planktonic cells, microplate-based abiotic biofilms, and epithelium-based biotic biofilms. Formation of persister cells byC. albicansin different growth modes was also quantified and compared. Results C. albicanswild-type reference strains and clinical isolates, but not the biofilm-defective mutants, formed a significant number of biotic biofilms on the vaginal epithelium of mice and infiltrated the epithelium. Biofilm formation and epithelial invasion induced local inflammatory responses and histopathological changes in the vaginal epithelium including neutrophil infiltration and subcorneal microabscesses. Biofilm growth on the vaginal epithelium also led to high resistance to antifungal treatments and promoted the formation of antifungal-tolerant persister cells. Conclusion This study comprehensively assessed biofilm-related microbial strategies thatC. albicansuses in vaginal candidiasis and provided experimental evidence to support the important role of biofilm formation in the histopathogenesis of vaginal candidiasis and the recalcitrance of the infection to antifungal treatment.