Effects of CTR4 deletion on virulence and stress response in Cryptococcus neoformans.
Roles of the high-affinity copper transporter Ctr4 in the virulence of Cryptococcus neoformans remain to be fully determined. Here we demonstrate that Ctr4 plays a necessary role in virulence and tolerance to a number of stress conditions. We first observed, with the method of flame atomic absorption spectrometry, that deletion of CTR4 resulted in a significant decrease in intracellular copper level, confirming the role of Ctr4 as a copper transporter in C. neoformans. Furthermore, CTR4 was critical for the yeast to survive at both elevated and low temperatures, as the growth rate of the ctr4Δ mutant at 4 and 37 °C was significantly decreased. The mutant ctr4Δ also exhibited hypersensitivity to osmotic stress imposed by 2 M NaCl or KCl, indicating the possible crosstalk of Ctr4 with the HOG signalling pathway. Moreover, cell wall and plasma membrane integrity appeared to be impaired in the ctr4Δ strain. The virulence of ctr4Δ in two mouse cryptococcosis models was remarkably reduced either via an intranasal or intravenous inoculation. Our work confirms the roles of Ctr4 in virulence and copper homeostasis as well as other additional novel functions.
National Key Program of Microbiology, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Ping
P
Zhang
National Key Program of Microbiology, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Defa
D
Zhang
National Key Program of Microbiology, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Xueru
X
Zhao
National Key Program of Microbiology, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Dongsheng
D
Wei
National Key Program of Microbiology, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Yu
Y
Wang
National Key Program of Microbiology, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071, China. zhu11187@bnu.edu.cn.|Institute of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, China. zhu11187@bnu.edu.cn.
Xudong
X
Zhu
D000818:Animals; D027682:Cation Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D003453:Cryptococcosis / Q000382:microbiology* / Q000473:pathology; D003455:Cryptococcus neoformans / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D004195:Disease Models, Animal; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009997:Osmotic Pressure / Q000502:physiology; D017384:Sequence Deletion; D015398:Signal Transduction; D014774:Virulence
D027682:Cation Transport Proteins; D005656:Fungal Proteins
CTR4; Copper uptake; Cryptococcus neoformans; Osmolality; Virulence