Abstract:pH-responsive transcription factors of the Rim101/PacC family govern virulence in many fungal pathogens. These family members control expression of target genes with diverse functions in growth, morphology, and environmental adaptation, so the mechanistic relationship between Rim101/PacC and infection is unclear. We have focused on Rim101 from Candida albicans, which we find to be required for virulence in an oropharyngeal candidiasis (OPC) model. Rim101 affects the yeast-hyphal morphological transition, a major virulence requirement in disseminated infection models. However, virulence in the OPC model is independent of the yeast-hyphal transition because it is unaffected by an nrg1 mutation, which prevents formation of yeast cells. Here we have identified Rim101 target genes in an nrg1Delta/Delta mutant background and surveyed function using an overexpression-rescue approach. Increased expression of Rim101 target genes ALS3, CHT2, PGA7/RBT6, SKN1, or ZRT1 can partially restore pathogenic interaction of a rim101Delta/Deltamutant with oral epithelial cells. Four of these five genes govern cell wall structure. Our results indicate that Rim101-dependent cell wall alteration contributes to C. albicans pathogenic interactions with oral epithelial cells, independently of cell morphology.

Status: Published Type: Journal Article PubMed ID: 18627379

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#1-10(ALS3-HGT1) #11-20(HOL4-PGA7) #21-26(PHR1-ZRT101)

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