title: Candida glabrata STE12 is required for wild-type levels of virulence and nitrogen starvation induced filamentation.
abstract: The highly conserved fungal Ste12 transcription factor family of proteins play critical roles in the regulation of many cellular processes including mating, cell wall biosynthesis, filamentation and invasive growth. They are also important mediators of fungal virulence. The Candida glabrata STE12 homologue was cloned. The encoded protein has a single DNA binding homeodomain but lacks both a C2H2 zinc finger DNA binding domain and an apparent Dig1/Dig2 regulatory motif. Candida glabrata STE12 can functionally complement the nitrogen starvation induced filamentation and mating defects of Saccharomyces cerevisiae ste12 mutants. We also show that C. glabrata STE12 is required for nitrogen starvation-induced filamentation as ste12 mutants rarely produce pseudohyphae on nitrogen depleted media. Finally we describe a novel murine model of C. glabrata systemic disease and use this to demonstrate that C. glabrata ste12 mutants, although still able to cause disease, are attenuated for virulence compared with STE12 reconstituted strains. Candida glabrata STE12 is therefore the first virulence factor encoding gene to be described in this increasingly important fungal pathogen.
authors: Department of Infectious Diseases & Microbiology, Imperial College London, Du Cane Road, London, W12 0NN, UK.
authors: Ana-Maria
authors: AM
authors: Calcagno
authors: Elaine
authors: E
authors: Bignell
authors: Peter
authors: P
authors: Warn
authors: Michael D
authors: MD
authors: Jones
authors: David W
authors: DW
authors: Denning
authors: Fritz A
authors: FA
authors: Mühlschlegel
authors: Thomas R
authors: TR
authors: Rogers
authors: Ken
authors: K
authors: Haynes
mesh_terms: D000818:Animals; D041221:Candida glabrata / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology; D005656:Fungal Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009584:Nitrogen / Q000378:metabolism*; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D037521:Virulence Factors; D009584:Nitrogen