title: Convergent Regulation of Candida albicans Aft2 and Czf1 in Invasive and Opaque Filamentation.
abstract: Candida albicans is the most common fungal pathogen of mucosal infections and invasive diseases in immuno-compromised humans. The abilities of yeast-hyphal growth and white-opaque switching affect C. albicans physiology and virulence. Here, we showed that C. albicans Aft2 regulator was required for embedded filamentous growth and opaque cell-type formation. Under low-temperature matrix embedded conditions, Aft2 functioned downstream of Czf1-mediated pathway and was required for invasive filamentation. Moreover, deletion of AFT2 significantly reduced opaque cell-type formation under N-acetylglucosamine (GlcNAc) inducing conditions. Ectopic expression of CZF1 slightly increased the white-opaque switching frequency in the aft2Δ/Δ mutant, but did not completely restore to wild-type levels, suggesting that Czf1 at least partially bypassed the essential requirement for Aft2 in response to opaque-inducing cues. In addition, multiple environmental cues altered AFT2 mRNA and protein levels, such as low temperature, physical environment and GlcNAc. Although the absence of Czf1 or Efg1 also increased the expression level of AFT2 gene, deletion of CZF1 remarkably reduced the stability of Aft2 protein. Furthermore, C. albicans Aft2 physically interacted with Czf1 under all tested conditions, whereas the interaction between Aft2 and Efg1 was barely detectable under embedded conditions, supporting the hypothesis that Aft2, together with Czf1, contributed to activate filamentous growth by antagonizing Efg1-mediated repression under matrix-embedded conditions.
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.|Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Dong
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Qi-Lin
authors.initials: QL
authors.lastname: Yu
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Jia
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Yu-Lu
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Lai-Jun
authors.initials: LJ
authors.lastname: Xing
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Li
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology; D051698:Activating Transcription Factor 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D055550:Protein Stability; D015398:Signal Transduction; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051698:Activating Transcription Factor 2; D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D014157:Transcription Factors; C077336:CZF1 protein, Candida albicans; D000117:Acetylglucosamine
keywords: Aft2; Candida albicans; FILAMENTOUS GROWTH; INVASIVE FILAMENTATION; WHITE-OPAQUE SWITCHING