title: Distinct roles of Candida albicans-specific genes in host-pathogen interactions.
abstract: Human fungal pathogens are distributed throughout their kingdom, suggesting that pathogenic potential evolved independently. Candida albicans is the most virulent member of the CUG clade of yeasts and a common cause of both superficial and invasive infections. We therefore hypothesized that C. albicans possesses distinct pathogenicity mechanisms. In silico genome subtraction and comparative transcriptional analysis identified a total of 65 C. albicans-specific genes (ASGs) expressed during infection. Phenotypic characterization of six ASG-null mutants demonstrated that these genes are dispensable for in vitro growth but play defined roles in host-pathogen interactions. Based on these analyses, we investigated two ASGs in greater detail. An orf19.6688Δ mutant was found to be fully virulent in a mouse model of disseminated candidiasis and to induce higher levels of the proinflammatory cytokine interleukin-1β (IL-1β) following incubation with murine macrophages. A pga16Δ mutant, on the other hand, exhibited attenuated virulence. Moreover, we provide evidence that secondary filamentation events (multiple hyphae emerging from a mother cell and hyphal branching) contribute to pathogenicity: PGA16 deletion did not influence primary hypha formation or extension following contact with epithelial cells; however, multiple hyphae and hyphal branching were strongly reduced. Significantly, these hyphae failed to damage host cells as effectively as the multiple hypha structures formed by wild-type C. albicans cells. Together, our data show that species-specific genes of a eukaryotic pathogen can play important roles in pathogenicity.
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany Duncan.Wilson@abdn.ac.uk.
authors.forename: Duncan
authors.initials: D
authors.lastname: Wilson
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany.
authors.forename: François L
authors.initials: FL
authors.lastname: Mayer
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany.
authors.forename: Pedro
authors.initials: P
authors.lastname: Miramón
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany.
authors.forename: Francesco
authors.initials: F
authors.lastname: Citiulo
authors.affiliation: Research Group Microbial Immunology, Hans Knoell Institute, Jena, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Slesiona
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany Research Group Microbial Immunology, Hans Knoell Institute, Jena, Germany.
authors.forename: Ilse D
authors.initials: ID
authors.lastname: Jacobsen
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany Center for Sepsis Control and Care, Universitätsklinikum, Jena, Germany Friedrich Schiller University, Jena, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism; D002177:Candidiasis / Q000382:microbiology*; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D054884:Host-Pathogen Interactions; D006801:Humans; D025301:Hyphae / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data
chemical_list: D005656:Fungal Proteins; D053583:Interleukin-1beta