Eca1, a Sarcoplasmic/Endoplasmic reticulum Ca2+-ATPase, is involved in stress tolerance and virulence in Cryptococcus neoformans
Eca1, a Sarcoplasmic/Endoplasmic reticulum Ca2+-ATPase, is involved in stress tolerance and virulence in Cryptococcus neoformans
复制标题
DOI：
10.1128/iai.01977-06
复制
发表时间：
2007-07-01
影响因子：
3.1
通讯作者：
Heitman, Joseph
中科院分区：
文献类型：
--
作者：
Fan, Weihua;Idnurm, Alexander;Heitman, Joseph
担子菌真菌病原体新型隐球菌适应于在土壤和环境中以及在哺乳动物宿主的独特环境中生存的挑战。在土壤阿米巴模型中分离出一种新型隐球菌突变体，其毒力增强，但在哺乳动物体温（37 ℃）下生长显著降低。这种突变表型是由ECAI基因中的插入引起的，ECAI基因编码肌质/内质网（ER）Ca 2 + -ATP酶（SERCA）型钙泵。感染小鼠巨噬细胞、阿米巴原虫（Castellanii阿米巴原虫）、线虫（秀丽隐杆线虫）和蜡螟（大蜡螟）幼虫表明，eca 1突变体在允许的生长温度下是毒性或超毒性的，但在37 ℃下是减毒的。缺失突变体缺乏整个ECA 1基因也高度敏感钙调磷酸酶抑制剂环孢素和FK 506和ER和渗透压应力。缺乏Eca 1和钙调神经磷酸酶催化亚基的eca 1 Delta cna 1 Delta突变体比单一突变体对高温和内质网应激更敏感，并且在C.在允许体外正常生长的温度下，对蜡螟幼虫的毒力减弱。Eca 1可能参与维持ER功能，从而与Ca 2+钙调神经磷酸酶信号传导平行地作用于胁迫耐受性和毒性。
The basidiomycetous fungal pathogen Cryptococcus neoformans is adapted to survive challenges in the soil and environment and within the unique setting of the mammalian host. A C neoformans mutant was isolated with enhanced virulence in a soil amoeba model that nevertheless exhibits dramatically reduced growth at mammalian body temperature (37 degrees C). This mutant phenotype results from an insertion in the ECAI gene, which encodes a sarcoplasmic/endoplasmic reticulum (ER) Ca2+ -ATPase (SERCA)-type calcium pump. Infection in murine macrophages, amoebae (Acanthamoeba castellanii), nematodes (Caenorhabditis elegans), and wax moth (Galleria mellonella) larvae revealed that the eca1 mutants are virulent or hypervirulent at permissive growth temperatures but attenuated at 37 degrees C. Deletion mutants lacking the entire ECA1 gene were also hypersensitive to the calcineurin inhibitors cyclosporin and FK506 and to ER and osmotic stresses. An eca1 Delta cna1 Delta mutant lacking both Eca1 and the calcineurin catalytic subunit was more sensitive to high temperature and ER stresses than the single mutants and exhibited reduced survival in C. elegans and attenuated virulence towards wax moth larvae at temperatures that permit normal growth in vitro. Eca1 is likely involved in maintaining ER function, thus contributing to stress tolerance and virulence acting in parallel with Ca2+ calcineurin signaling.