Yeast wall protein 1 of Candida albicans

Yeast wall protein 1 of Candida albicans
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DOI:
10.1099/mic.0.27663-0
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发表时间:
2005-05-01
期刊:
影响因子:
2.8
通讯作者:
Cutler, JE
Cutler, JE
中科院分区:
生物学4区
文献类型:
--
作者:
Granger, BL;Flenniken, ML;Cutler, JE

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白念珠菌酵母壁蛋白1(Ywp 1,又称Pga 24)是一个由533个氨基酸组成的多肽,其N端含有分泌信号,C端含有糖基化磷脂酰肌醇锚信号,中心区域富含丝氨酸和苏氨酸。在酵母培养物中,Ywp 1 p似乎共价连接到壁基质的葡聚糖,但是,随着培养物接近静止期,Ywp 1 p在培养基中积累,并且可以用二硫化物还原剂从细胞中提取。一个11 kDa的前肽Ywp 1 p也存在于这些可溶性馏分,它拥有唯一的N-聚糖Ywp 1 p,并作为一个有用的标记Ywp 1 p。编码全部或部分Ywp 1 p的DNA疫苗在小鼠中产生了分析有用的抗血清,但并没有增加播散性念珠菌病的存活时间。用荧光报告GFP替换YWP 1的编码序列显示,YWP 1的表达在酵母指数期生长期间最大,但在稳定期和表达后下调。当细胞外磷酸盐浓度低时,表达上调。两个YWP 1等位基因的同源重组的破坏导致生长,形态或毒力没有明显的变化,但YWP 1 p缺陷的芽生孢子表现出增加的粘附和生物膜形成,表明YWP 1 p可能促进酵母形式的C.白色念珠菌。
Yeast wall protein 1 (Ywp1, also called Pga24) of Candida albicans is predicted to be a 533 aa polypeptide with an N-terminal secretion signal, a C-terminal glycosylphosphaticlylinositol anchor signal and a central region rich in serine and threonine. In yeast cultures, Ywp1p appeared to be linked covalently to glucans of the wall matrix, but, as cultures approached stationary phase, Ywp1p accumulated in the medium and was extractable from cells with disulfide-reducing agents. An 11 kDa propeptide of Ywp1p was also present in these soluble fractions; it possessed the sole N-glycan of Ywp1p and served as a useful marker for Ywp1p. DNA vaccines encoding all or part of Ywp1p generated analytically useful antisera in mice, but did not increase survival times for disseminated candidiasis. Replacement of the coding sequence of YWP1 with the fluorescent reporter GFP revealed that expression of YWP1 is greatest during yeast exponential-phase growth, but downregulated in stationary phase and upon filamentation. Expression was upregulated when the extracellular phosphate concentration was low. Disruption by homologous recombination of both YWP1 alleles resulted in no obvious change in growth, morphology or virulence, but the Ywp1p-deficient blastoconidia exhibited increased adhesiveness and biofilm formation, suggesting that Ywp1p may promote dispersal of yeast forms of C. albicans.