Candida albicans VPS1 contributes to protease secretion, filamentation, and biofilm formation
Candida albicans VPS1 contributes to protease secretion, filamentation, and biofilm formation
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DOI：
10.1016/j.fgb.2008.01.001
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发表时间：
2008-06-01
影响因子：
3
通讯作者：
Lee, Samuel A.
中科院分区：
文献类型：
--
作者：
Bernardo, Stella M.;Khalique, Zachary;Lee, Samuel A.
为了研究白念珠菌空泡前分泌途径，我们克隆并分析了酿酒酵母空泡蛋白分选基因VPS 1的白念珠菌同源物。白色念珠菌VPS 1编码一个694个氨基酸的动力蛋白样GT3，与S.酿酒酵母Vps 1 p.携带白色念珠菌VPS 1的质粒补充了S.酿酒酵母vps 1无效突变体。为了研究VPS 1在白色念珠菌中的功能，通过删除VPS 1的第一个等位基因并将第二个等位基因置于四环素可调控启动子的控制下来产生条件突变株（tetR-VPS 1）。与强力霉素，tetR-VPS 1突变体是超敏感的氟康唑，但不是阿替霉素B，5-氟胞嘧啶，或非特异性渗透胁迫的亚抑制浓度。阻遏tetR-VPS 1突变体是缺陷的表达和分泌较少的胞外蛋白酶活性。生物膜的产生和生物膜内的降解显著减少。这些结果表明，白色念珠菌VPS 1在几个重要的毒力相关表型中具有关键作用。(c)2008年爱思唯尔公司All rights reserved.
To investigate the pre-vacuolar secretory pathway in Candida albicans, we cloned and analyzed the C albicans homolog of the Saccharomyces cerevisiae vacuolar protein sorting gene VPS1. C albicans VPS1 encodes a predicted 694-aa dynamin-like GTPase that is 73.3% similar to S. cerevisiae Vps1p. Plasmids bearing C albicans VPS1 complemented the temperature-sensitive growth, abnormal class F vacuolar morphology, and carboxypeptidase missorting of a S. cerevisiae vps1 null mutant. To study VPS1 function in C albicans, a conditional mutant strain (tetR-VPS1) was generated by deleting the first allele of VPS1 and placing the second allele under control of a tetracycline-regulatable promoter. With doxycycline, the tetR-VPS1 mutant was hyper-susceptible to sub-inhibitory concentrations of fluconazole, but not amphotericin B, 5-fluorocytosine, or non-specific osmotic stresses. The repressed tetR-VPS1 mutant was defective in filamentation and secreted less extracellular protease activity. Biofilm production and filamentation within the biofilm were markedly reduced. These results suggest that C albicans VPS1 has a key role in several important virulence-related phenotypes. (c) 2008 Elsevier Inc. All rights reserved.