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Sho1p衔接蛋白在机会性酵母葡萄牙念珠菌假菌丝发育、药物敏感性、渗透压耐受性及氧化应激适应中的作用

Role of Sho1p adaptor in the pseudohyphal development, drugs sensitivity, osmotolerance and oxidant stress adaptation in the opportunistic yeast Candida lusitaniae.

作者信息

Boisnard Stéphanie, Ruprich-Robert Gwenaël, Florent Martine, Da Silva Bruno, Chapeland-Leclerc Florence, Papon Nicolas

机构信息

Programme Chimiorésistance des Levures Pathogènes, EA209 Eucaryotes Pathogènes: Transports Membranaires et Chimiorésistance, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, 75006 Paris, France.

出版信息

Yeast. 2008 Nov;25(11):849-59. doi: 10.1002/yea.1636.

DOI:10.1002/yea.1636
PMID:19061190
Abstract

In yeast, external signals such as high osmolarity or oxidant conditions activate the high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) cascade pathway, which consists of two upstream branches, i.e. Sho1p and Sln1p and common downstream elements, including the Pbs2p MAPK kinase and the Hog1p MAPK. We recently showed that the Candida lusitaniae SLN1 gene, potentially encoding a histidine kinase receptor, is crucial for oxidative stress adaptation when the fungus grows as budding yeast and during the early steps of pseudohyphal development. In the current study, we characterized the SHO1 gene of this opportunistic fungus. Complete loss of SHO1 function causes profound defects in pseudohyphal differentiation, especially in high osmolarity and oxidative stress conditions, suggesting a crucial role of SHO1 in the pseudohyphae morphogenetic transitions. Moreover, when grown as budding yeast, the sho1Delta mutant revealed a sensitivity to compounds that interfere with the cell wall assembly, pointing to a potential role of Sho1p in cell wall biogenesis. However, the sho1Delta mutant does not display evident cell-wall architecture modifications, such as aggregation phenotypes. Although not hypersusceptible to antifungals of clinical relevance, the sho1Delta mutants are susceptible to the filamentous fungi-specific antifungals dicarboximides and phenylpyrroles. Finally, our findings highlight some significant phenotypic differences when the C. lusitaniae sho1Delta mutant is compared with the corresponding mutants described in Saccharomyces cerevisiae, Candida albicans and Aspergillus fumigatus.

摘要

在酵母中,诸如高渗透压或氧化应激条件等外部信号会激活高渗透压甘油(HOG)丝裂原活化蛋白激酶(MAPK)级联途径,该途径由两个上游分支,即Sho1p和Sln1p以及共同的下游元件组成,包括Pbs2p MAPK激酶和Hog1p MAPK。我们最近发现,葡萄牙念珠菌的SLN1基因可能编码一种组氨酸激酶受体,当该真菌以出芽酵母形式生长时以及在假菌丝发育的早期阶段,该基因对于氧化应激适应至关重要。在本研究中,我们对这种机会性真菌的SHO1基因进行了表征。SHO1功能的完全丧失会导致假菌丝分化出现严重缺陷,尤其是在高渗透压和氧化应激条件下,这表明SHO1在假菌丝形态发生转变中起关键作用。此外,当以出芽酵母形式生长时,sho1Delta突变体对干扰细胞壁组装的化合物表现出敏感性,这表明Sho1p在细胞壁生物合成中具有潜在作用。然而,sho1Delta突变体并未表现出明显的细胞壁结构修饰,如聚集表型。尽管对具有临床相关性的抗真菌药物不高度敏感,但sho1Delta突变体对丝状真菌特异性抗真菌药物二羧酰亚胺和苯基吡咯敏感。最后,我们的研究结果突出了将葡萄牙念珠菌sho1Delta突变体与酿酒酵母、白色念珠菌和烟曲霉中描述的相应突变体进行比较时的一些显著表型差异。

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