title: Role of the N-acetylglucosamine kinase (Hxk1) in the regulation of white-gray-opaque tristable phenotypic transitions in C. albicans.
abstract: The amino sugar N-acetylglucosamine (GlcNAc) is a host-related environmental cue and a potent inducer of morphological transitions in the human fungal pathogen Candida albicans. It has been well established that GlcNAc promotes white-to-opaque switching and yeast-to-hyphal growth transition primarily through the Ras-cAMP signaling pathway. As a commensal yeast of humans, C. albicans can efficiently use GlcNAc as the carbon source. In this study, we sought to investigate whether the catabolic pathway of GlcNAc is involved in the regulation of white-gray-opaque tristable transitions in C. albicans. Phenotypic switching assays demonstrated that deletion of the GlcNAc kinase gene, HXK1, induced the gray and opaque phenotypes in a SC5314 background strain, which is heterozygous at the mating type locus (a/α) and is unable to switch to the gray or opaque phenotype under standard culture conditions. Cell type-enriched genes were exclusively expressed in the white, gray, and opaque cells of the hxk1/hxk1 mutant. Mating assays demonstrated that, similar to the counterparts of BJ1097 (a natural white-gray-opaque switchable strain), opaque cells of the hxk1/hxk1 mutant (Δ/α) mated more efficiently than white and gray cells. The transcription factors, Wor1 and Efg1, are required for the development of the opaque and white cell types in the hxk1/hxk1 mutant, respectively. However, deletion of the GlcNAc-specific transporter gene (NGT1), GlcNAc-6-phosphate deacetylase gene (DAC1), and glucosamine-6-phosphate deaminase gene (NAG1) in the same background strain had no obvious effect on white-gray-opaque transitions. Our findings suggest that the GlcNAc kinase, Hxk1, may function as a morphological regulator independent on its catabolic role in C. albicans.
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guobo
authors.initials: G
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Han
authors.initials: H
authors.lastname: Du
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: huanggh@im.ac.cn.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Huang
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D049770:Genes, Mating Type, Fungal / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D010858:Pigmentation / Q000235:genetics*; D017354:Point Mutation; D015398:Signal Transduction
chemical_list: D005656:Fungal Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C018716:N-acetylglucosamine kinase; D000117:Acetylglucosamine
keywords: Candida albicans; Efg1; GlcNAc metabolism; Hxk1; Phenotypic switching; Wor1