Citiulo, Francisco

Hube, Bernhard

Jacobsen, Ilse D

Mayer, François L

Miramón, Pedro

Slesiona, Silvia

Wilson, Duncan

Eukaryotic Cell

PubMed

Aberdeen University Research

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.
              a
              lbicans
            
            -
            s
            pecific
            g
            enes (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
            pga16
            Δ 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.
          </jats:p

Distinct roles of Candida albicans-specific genes in host-pathogen interactions

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