title: Transcription factor Nrg1 mediates capsule formation, stress response, and pathogenesis in Cryptococcus neoformans.
abstract: The Cryptococcus neoformans NRG1 gene was identified using gene microarrays to define putative transcription factor genes regulated by the cyclic AMP (cAMP) signal transduction pathway. Disruption of NRG1 results in delayed capsule formation and mating, two phenotypes that are directly controlled by cAMP signaling. Putative targets of the Nrg1 transcription factor were identified using a second genome microarray to define differences in the transcriptomes of the wild-type and nrg1 mutant strains. These experiments implicate Nrg1 in the transcriptional control of multiple genes involved in carbohydrate metabolism and substrate oxidation, as well as the UGD1 gene encoding a UDP-glucose dehydrogenase required for polysaccharide capsule production and cell wall integrity. In addition to being under transcriptional control of the cAMP pathway, Nrg1 contains a putative protein kinase A phosphorylation site; mutation of this motif results in reduced Nrg1 activity. Consistent with prior studies in hypocapsular mutants, the nrg1 mutant strain is attenuated in an animal model of disseminated cryptococcal disease.
authors.affiliation: Department of Medicine and Molecular Genetics/Microbiology, Duke University Medical Center 3355, Durham, North Carolina 27710, USA.
authors.forename: Kari L
authors.initials: KL
authors.lastname: Cramer
authors.forename: Quincy D
authors.initials: QD
authors.lastname: Gerrald
authors.forename: Connie B
authors.initials: CB
authors.lastname: Nichols
authors.forename: Michael S
authors.initials: MS
authors.lastname: Price
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Alspaugh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001682:Biological Availability; D002473:Cell Wall / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000378:metabolism* / Q000472:pathogenicity* / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D018390:Gene Targeting; D049770:Genes, Mating Type, Fungal; D005947:Glucose / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D030781:Organisms, Genetically Modified / Q000002:abnormalities; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose