title: Identification of a novel response regulator, Crr1, that is required for hydrogen peroxide resistance in Candida albicans.
abstract: Candida albicans colonises numerous niches within humans and thus its success as a pathogen is dependent on its ability to adapt to diverse growth environments within the host. Two component signal transduction is a common mechanism by which bacteria respond to environmental stimuli and, although less common, two component-related pathways have also been characterised in fungi. Here we report the identification and characterisation of a novel two component response regulator protein in C. albicans which we have named CRR1 (Candida Response Regulator 1). Crr1 contains a receiver domain characteristic of response regulator proteins, including the conserved aspartate that receives phosphate from an upstream histidine kinase. Significantly, orthologues of CRR1 are present only in fungi belonging to the Candida CTG clade. Deletion of the C. albicans CRR1 gene, or mutation of the predicted phospho-aspartate, causes increased sensitivity of cells to the oxidising agent hydrogen peroxide. Crr1 is present in both the cytoplasm and nucleus, and this localisation is unaffected by oxidative stress or mutation of the predicted phospho-aspartate. Furthermore, unlike the Ssk1 response regulator, Crr1 is not required for the hydrogen peroxide-induced activation of the Hog1 stress-activated protein kinase pathway, or for the virulence of C. albicans in a mouse model of systemic disease. Taken together, our data suggest that Crr1, a novel response regulator restricted to the Candida CTG clade, regulates the response of C. albicans cells to hydrogen peroxide in a Hog1-independent manner that requires the function of the conserved phospho-aspartate.
authors.affiliation: Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Bruce
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Rodgers
authors.forename: Alessandra
authors.initials: A
authors.lastname: da Silva Dantas
authors.forename: Donna M
authors.initials: DM
authors.lastname: MacCallum
authors.forename: Brian A
authors.initials: BA
authors.lastname: Morgan
authors.forename: Janet
authors.initials: J
authors.lastname: Quinn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides / Q000737:chemistry; D018384:Oxidative Stress; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D009841:Oligonucleotides; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D001224:Aspartic Acid; D006861:Hydrogen Peroxide; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases