title: Functional characterization of the small heat shock protein Hsp12p from Candida albicans.
abstract: Hsp12p is considered to be a small heat shock protein and conserved among fungal species. To investigate the expression of this heat shock protein in the fungal pathogen Candida albicans we developed an anti-CaHsp12p antibody. We show that this protein is induced during stationary phase growth and under stress conditions including heat shock, osmotic, oxidative and heavy metal stress. Furthermore, we find that CaHsp12p expression is influenced by the quorum sensing molecule farnesol, the change of CO(2) concentration and pH. Notably we show that the key transcription factor Efg1p acts as a positive regulator of CaHsp12p in response to heat shock and oxidative stress and demonstrate that CaHsp12p expression is additionally modulated by Hog1p and the cAMP-PKA signaling pathway. To study the function of Hsp12p in C. albicans we generated a null mutant, in which all four CaHSP12 genes have been deleted. Phenotypic analysis of the strain shows that CaHSP12 is not essential for stress resistance, morphogenesis or virulence when tested in a Drosophila model of infection. However, when overexpressed, CaHSP12 significantly enhanced cell-cell adhesion, germ tube formation and susceptibility to azole antifungal agents whilst desensitizing C. albicans to the quorum sensing molecule farnesol.
authors.affiliation: School of Biosciences, University of Kent, Canterbury, Kent, United Kingdom.
authors.forename: Man-Shun
authors.initials: MS
authors.lastname: Fu
authors.forename: Luisa
authors.initials: L
authors.lastname: De Sordi
authors.forename: Fritz A
authors.initials: FA
authors.lastname: Mühlschlegel
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D018387:Codon, Initiator / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005204:Farnesol / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics; D050888:Heat-Shock Proteins, Small / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response / Q000187:drug effects / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009997:Osmotic Pressure / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011090:Polyenes / Q000494:pharmacology; D053038:Quorum Sensing / Q000187:drug effects / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013045:Species Specificity; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D014774:Virulence / Q000187:drug effects / Q000235:genetics
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D018387:Codon, Initiator; D005656:Fungal Proteins; D050888:Heat-Shock Proteins, Small; D011090:Polyenes; D005204:Farnesol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases