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钙调磷酸酶靶蛋白 7 在白念珠菌离子稳态调节、药物耐受、丝状形成和毒力中的功能。

Functions of CaPhm7 in the regulation of ion homeostasis, drug tolerance, filamentation and virulence in Candida albicans.

机构信息

Laboratory for Yeast Molecular and Cell Biology, the Research Center of Fermentation Technology, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo, 255000, China.

出版信息

BMC Microbiol. 2018 Jun 4;18(1):49. doi: 10.1186/s12866-018-1193-9.

Abstract

BACKGROUND

Calcium-permeable transient receptor potential (TRP) channels exist in eukaryotic cells from yeasts to animals and plants. and they act as sensors for various stresses. Arabidopsis thaliana calcium permeable stress-gated cation channel 1 (AtCSC1) was the first plant calcium-permeable TRP to be described and can be activated by hyperosmotic shock. Candida albicans CaPHM7 is one of the sequence homologs of AtCSC1, but its function remains unknown.

RESULTS

We show here that CaPhm7 is localized to the plasma membrane in both the yeast and hyphal cells of C. albicans. C. albicans cells lacking CaPHM7 are sensitive to SDS and ketoconazole but tolerant to rapamycin and zinc. In addition, deletion of CaPHM7 leads to a filamentation defect, reduced colony growth and attenuated virulence in the mouse model of systemic infection.

CONCLUSIONS

CaPhm7 is involved in the regulation of ion homeostasis, drug tolerance, filamentation and virulence in this important human fungal pathogen. CaPhm7 could be a potential target of antifungal drugs.

摘要

背景

钙通透性瞬时受体电位(TRP)通道存在于从酵母到动植物的真核细胞中,它们充当各种应激的传感器。拟南芥钙通透性应激门控阳离子通道 1(AtCSC1)是第一个被描述的植物钙通透性 TRP,可被高渗冲击激活。白色念珠菌 CaPHM7 是 AtCSC1 的序列同源物之一,但它的功能尚不清楚。

结果

我们在这里表明,CaPhm7 在白色念珠菌的酵母和菌丝细胞中定位于质膜。缺乏 CaPHM7 的白色念珠菌细胞对 SDS 和酮康唑敏感,但对雷帕霉素和锌耐受。此外,CaPHM7 的缺失导致菌丝形成缺陷、菌落生长减少和在系统性感染的小鼠模型中毒力减弱。

结论

CaPhm7 参与调节这种重要的人类真菌病原体中的离子稳态、药物耐受性、菌丝形成和毒力。CaPhm7 可能是抗真菌药物的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4634/5987382/23d3dcf35c1d/12866_2018_1193_Fig1_HTML.jpg

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