Genetic interactions between Rch1 and the high-affinity calcium influx system Cch1/Mid1/Ecm7 in the regulation of calcium homeostasis, drug tolerance, hyphal development and virulence in Candida albicans.
The high-affinity calcium influx system (HACS) consisted of CaCch1, CaMid1 and CaEcm7 controls calcium influx into the cell in response to environmental stimuli. The plasma membrane protein CaRch1 is a negative regulator of calcium influx in Candida albicans. In this study, we show that deletion of any of the HACS components suppresses the calcium hypersensitivity of, and the elevated activation level of calcium/calcineurin signaling in, C. albicans cells lacking CaRCH1. In contrast, CaRCH1 is epistatic to the HACS system in the tolerance of antifungal drugs. In addition, cells lacking CaRCH1 are sensitive to tunicamycin, show a delay in in vitro filamentation and an altered colony surface morphology, and are attenuated in virulence in a mouse systemic model. Cells lacking CaCCH1 and CaMID1, but not CaECM7, are sensitive to tunicamycin. Deletion of CaRCH1 increases the tunicamycin sensitivity of cells lacking CaECM7 or CaMID1, but not CaCCH1. Furthermore, deletion of CaRCH1 suppresses the defect in hyphal development due to the deletion of CaCCH1 or CaECM7, and increases the virulence of cells lacking any of the HACS components. Therefore, CaRch1 genetically interacts with the HACS components in different fashions for these functions.
The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China College of Life Sciences, Huaibei Normal University, Huaibei 235000, Anhui, China.
Dayong
D
Xu
School of Medicine, Jiangnan University, Wuxi 214122, China.
Jianqing
J
Cheng
The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Chunlei
C
Cao
The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Litong
L
Wang
The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China linghuojiang@hotmail.com.
Linghuo
L
Jiang
D000818:Animals; 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; D004195:Disease Models, Animal; D004361:Drug Tolerance; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D051379:Mice; D013312:Stress, Physiological; D014774:Virulence; D028901:alpha Karyopherins / Q000378:metabolism*
D015220:Calcium Channels; D028901:alpha Karyopherins; C087978:karyopherin alpha 2; D002118:Calcium
cch1; ecm7; ketoconazole; mid1; rch1; tunicamycin