title: Genetic interactions between the Golgi Ca2+/H+ exchanger Gdt1 and the plasma membrane calcium channel Cch1/Mid1 in the regulation of calcium homeostasis, stress response and virulence in Candida albicans.
abstract: The Golgi-localized Saccharomyces cerevisiae ScGdt1 is a member of the cation/Ca(2+) exchanger superfamily. We show here that Candida albicans CaGdt1 is the functional homolog of ScGdt1 in calcium sensitivity, and shows genetic interactions with CaCch1 or CaMid1 in response to ER stresses. In addition, similar to ScCCH1 and ScMID1, deletion of either CaCCH1 or CaMID1 leads to a growth sensitivity of cells to cold stress, which can be suppressed by deletion of CaGDT1. Furthermore, deletion of CaCCH1 leads to a severe delay in filamentation of C. albicans cells, and this defect is abolished by deletion of CaGDT1. In contrast, CaGDT1 does not show genetic interaction with CaMID1 in filamentation. Interestingly, C. albicans cells lacking both CaMID1 and CaGDT1 exhibit an intermediate virulence between C. albicans cells lacking CaCCH1 (non-virulent) and C. albicans cells lacking CaGDT1 (partially virulent), while C. albicans cells lacking both CaCCH1 and CaGDT1 are not virulent in a mouse model of systemic candidiasis. Therefore, CaGdt1 genetically interacts with the plasma membrane calcium channel, CaCch1/CaMid1, in the response of C. albicans cells to cold and ER stresses and antifungal drug challenge as well as in filamentation and virulence.
authors.affiliation: The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Medicine, Jiangnan University, Wuxi 214122, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Xu
authors.affiliation: The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China linghuojiang@jiangnan.edu.cn.
authors.forename: Linghuo
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002176:Candida albicans / Q000166:cytology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology; D003080:Cold Temperature; D004195:Disease Models, Animal; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006056:Golgi Apparatus / Q000201:enzymology*; D006706:Homeostasis; D051379:Mice; D025941:Protein Interaction Mapping; D013312:Stress, Physiological; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D015220:Calcium Channels; D002118:Calcium
keywords: Cch1; ER stress; Gdt11; Mid1; cold stress; virulence