title: Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis.
abstract: Denture stomatitis (DS) is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by Candida albicans, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating Candida infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using C. albicans or mutants defective in morphogenesis (efg1-/-) or biofilm formation (bcr1-/-). For in vivo analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type C. albicans, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate), body weight and tissue damage (LDH) for up to 8 weeks. C. albicans wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under in vitro, ex vivo and in vivo conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM). In contrast, both efg1-/- and bcr1-/- mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with efg1-/-, but not bcr1-/-, compared to controls. Finally, rats inoculated with efg1-/- and bcr1-/- mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in C. albicans, have pivotal roles in pathogenesis of DS.
authors.affiliation: Department of Oral and Craniofacial Biology, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Junko
authors.initials: J
authors.lastname: Yano
authors.affiliation: Department of Prosthodontics, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Alika
authors.initials: A
authors.lastname: Yu
authors.affiliation: Department of Oral and Craniofacial Biology, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Fidel
authors.affiliation: Department of Oral and Craniofacial Biology, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.|Department of Prosthodontics, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Mairi C
authors.initials: MC
authors.lastname: Noverr
mesh_terms: D000818:Animals; D018441:Biofilms; D002176:Candida albicans / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology*; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009061:Mouth Mucosa / Q000382:microbiology; D051381:Rats; D013282:Stomatitis, Denture / Q000382:microbiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D014157:Transcription Factors