title: Transcriptional response of Candida albicans to nitric oxide and the role of the YHB1 gene in nitrosative stress and virulence.
abstract: Here, we investigate how Candida albicans, the most prevalent human fungal pathogen, protects itself from nitric oxide (*NO), an antimicrobial compound produced by the innate immune system. We show that exposure of C. albicans to *NO elicits a reproducible and specific transcriptional response as determined by genome-wide microarray analysis. Many genes are transiently induced or repressed by *NO, whereas a set of nine genes remain at elevated levels during *NO exposure. The most highly induced gene in this latter category is YHB1, a flavohemoglobin that detoxifies *NO in C. albicans and other microbes. We show that C. albicans strains deleted for YHB1 have two phenotypes in vitro; they are hypersensitive to *NO and they are hyperfilamentous. In a mouse model of disseminated candidiasis, a YHB1 deleted C. albicans strain shows moderately attenuated virulence, but the virulence defect is not suppressed by deletion of the host NOS2 gene. These results suggest that *NO production is not a prime determinant of virulence in the mouse tail vein model of candidiasis and that the attenuated virulence of a yhb1delta/yhb1delta strain is attributable to a defect other than its reduced ability to detoxify *NO.
authors: Department of Microbiology and Immunology, University of California-San Francisco, San Francisco, CA 94143, USA.
authors: Bethann S
authors: BS
authors: Hromatka
authors: Suzanne M
authors: SM
authors: Noble
authors: Alexander D
authors: AD
authors: Johnson
mesh_terms: D000475:Alkenes / Q000494:pharmacology; D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D002177:Candidiasis / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D000475:Alkenes; D005656:Fungal Proteins; D020030:Nitric Oxide Donors; C453079:dipropylenetriamine-NONOate; D009569:Nitric Oxide