Candida glabrata Has No Enhancing Role in the Pathogenesis of Candida-Associated Denture Stomatitis in a Rat Model

摘要

Denture stomatitis (DS) is a condition characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. Candida- associated DS is predominantly caused by Candida albicans , a dimorphic fungus that readily colonizes and forms biofilms on denture materials. Previous studies showed a requirement for Candida biofilm formation on both palate and dentures in infection and identified fungal morphogenic transcription factors, Efg1 and Bcr1, as key players in DS pathogenesis. While both C. albicans and Candida glabrata are frequently coisolated in mucosal candidiasis, a pathogenic role for C. glabrata in DS remains unknown. Using an established rat model of DS, we sought to determine whether C. glabrata alone or coinoculation with C. albicans establishes colonization and causes palatal tissue damage and inflammation. Rats fitted with custom dentures were inoculated with C. albicans and/or C. glabrata and monitored over a 4-week period for fungal burden (denture/palate), changes in body weight, and tissue damage via lactate dehydrogenase (LDH) release as well as palatal staining by hematoxylin and eosin (H&E) and immunohistochemistry for myeloperoxidase (MPO) as measures of inflammation. C. glabrata colonized the denture/palate similarly to C. albicans . In contrast to C. albicans , colonization by C. glabrata resulted in minimal changes in body weight, palatal LDH release, and MPO expression. Coinoculation with both species had no obvious modulation of C. albicans -mediated pathogenic effects. These data suggest that C. glabrata readily establishes colonization on denture and palate but has no apparent role for inducing/enhancing C. albicans pathogenesis in DS. IMPORTANCE Many denture wearers suffer from Candida -associated denture stomatitis (DS), a fungal infection of the hard palate in contact with dentures. Biofilm formation by Candida albicans on denture/palate surfaces is considered a central process in the infection onset. Although Candida glabrata is frequently coisolated with C. albicans , its role in DS pathogenesis is unknown. We show here, using a contemporary rat model that employed a patented intraoral denture system, that C. glabrata established stable colonization on the denture/palate. However, in contrast to C. albicans inoculated rats, rats inoculated with C. glabrata exhibited minimal changes in weight gain or palatal tissue damage. Likewise, coinoculation with the two Candida species resulted in no exacerbation of C. albicans -induced DS pathology. Together, our findings indicate that C. glabrata has no inducing/enhancing role in DS pathogenesis.