title: Comparative transcript profiling of Candida albicans and Candida dubliniensis identifies SFL2, a C. albicans gene required for virulence in a reconstituted epithelial infection model.
abstract: Candida albicans and Candida dubliniensis are closely related species displaying differences in virulence and genome content, therefore providing potential opportunities to identify novel C. albicans virulence genes. C. albicans gene arrays were used for comparative analysis of global gene expression in the two species in reconstituted human oral epithelium (RHE). C. albicans (SC5314) showed upregulation of hypha-specific and virulence genes within 30 min postinoculation, coinciding with rapid induction of filamentation and increased RHE damage. C. dubliniensis (CD36) showed no detectable upregulation of hypha-specific genes, grew as yeast, and caused limited RHE damage. Several genes absent or highly divergent in C. dubliniensis were upregulated in C. albicans. One such gene, SFL2 (orf19.3969), encoding a putative heat shock factor, was deleted in C. albicans. DeltaDeltasfl2 cells failed to filament under a range of hypha-inducing conditions and exhibited greatly reduced RHE damage, reversed by reintroduction of SFL2 into the DeltaDeltasfl2 strain. Moreover, SFL2 overexpression in C. albicans triggered hyphal morphogenesis. Although SFL2 deletion had no apparent effect on host survival in the murine model of systemic infection, DeltaDeltasfl2 strain-infected kidney tissues contained only yeast cells. These results suggest a role for SFL2 in morphogenesis and an indirect role in C. albicans pathogenesis in epithelial tissues.
authors.affiliation: Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental School and Hospital, University of Dublin, Trinity College, Dublin 2, Ireland.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Spiering
authors.forename: Gary P
authors.initials: GP
authors.lastname: Moran
authors.forename: Murielle
authors.initials: M
authors.lastname: Chauvel
authors.forename: Donna M
authors.initials: DM
authors.lastname: Maccallum
authors.forename: Judy
authors.initials: J
authors.lastname: Higgins
authors.forename: Karsten
authors.initials: K
authors.lastname: Hokamp
authors.forename: Tim
authors.initials: T
authors.lastname: Yeomans
authors.forename: Christophe
authors.initials: C
authors.lastname: d'Enfert
authors.forename: David C
authors.initials: DC
authors.lastname: Coleman
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D002175:Candida / Q000235:genetics* / Q000472:pathogenicity; D002176:Candida albicans / Q000235:genetics* / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics*; D016681:Genome, Fungal; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
chemical_list: D005656:Fungal Proteins