title: Identification of the cell targets important for propolis-induced cell death in Candida albicans.
abstract: Candida albicans is the most common fungal pathogen of humans, forming both commensal and opportunistic pathogenic interactions, causing a variety of skin and soft tissue infections in healthy people. In immunocompromised patients C. albicans can result in invasive, systemic infections that are associated with a high incidence of mortality. Propolis is a complex mixture of several resinous substances which are collected from plants by bees. Here, we demonstrated the fungicidal activity of propolis against all three morphogenetic types of C. albicans and that propolis-induced cell death was mediated via metacaspase and Ras signaling. To identify genes that were involved in propolis tolerance, we screened ~800 C. albicans homozygous deletion mutants for decreased tolerance to propolis. Fifty-one mutant strains were identified as being hypersensitive to propolis including seventeen genes involved in cell adhesion, biofilm formation, filamentous growth, phenotypic switching and pathogenesis (HST7, GIN4, VPS34, HOG1, ISW2, SUV3, MDS3, HDA2, KAR3, YHB1, NUP85, CDC10, MNN9, ACE2, FKH2, and SNF5). We validated these results by showing that propolis inhibited the transition from yeast-like to hyphal growth. Propolis was shown to contain compounds that conferred fluorescent properties to C. albicans cells. Moreover, we have shown that a topical pharmaceutical preparation, based upon propolis, was able to control C. albicans infections in a mouse model for vulvovaginal candidiasis. Our results strongly indicate that propolis could be used as a strategy for controlling candidiasis.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Patrícia Alves
authors.initials: PA
authors.lastname: de Castro
authors.forename: Vinícius Leite Pedro
authors.initials: VL
authors.lastname: Bom
authors.forename: Neil Andrew
authors.initials: NA
authors.lastname: Brown
authors.forename: Ricardo Sérgio Couto
authors.initials: RS
authors.lastname: de Almeida
authors.forename: Leandra Naira Zambelli
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Marcela
authors.initials: M
authors.lastname: Savoldi
authors.forename: Maria Helena S
authors.initials: MH
authors.lastname: Goldman
authors.forename: Andresa A
authors.initials: AA
authors.lastname: Berretta
authors.forename: Gustavo Henrique
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics*; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy* / Q000382:microbiology; D020169:Caspases / Q000378:metabolism; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011429:Propolis / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D000935:Antifungal Agents; D011429:Propolis; D020169:Caspases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Candida albicans; Deletion mutants; Propolis; Vulvovaginal candidiasis