Morphogenesis, adhesive properties, and antifungal resistance depend on the Pmt6 protein mannosyltransferase in the fungal pathogen Candida albicans
Morphogenesis, adhesive properties, and antifungal resistance depend on the Pmt6 protein mannosyltransferase in the fungal pathogen Candida albicans
复制标题
DOI：
10.1128/jb.182.11.3063-3071.2000
复制
发表时间：
2000-06-01
影响因子：
3.2
通讯作者：
Ernst, J
中科院分区：
文献类型：
--
作者：
Timpel, C;Zink, S;Ernst, J
蛋白甘露糖基转移酶（Pmt蛋白）启动真菌分泌蛋白的O糖基化。我们对编码白色念珠菌第二Pmt蛋白的PMT6进行了鉴定，Pmt6p的残基与白色念珠菌Pmt1p和酿酒酵母Pmt6p的残基分别相同21%和42%。缺乏一个或两个PMT6等位基因的突变体生长正常，在细胞提取物中含有正常的Pmt酶活性，但表现出包括菌丝形成部分阻断（二态性）和对湿霉素b超敏感的表型。这种形态发生缺陷可以通过过量产生已知的信号通路成分来抑制，包括Cek1p、Cph1p、Tpk2p和Efg1p，这表明Pmt6p靶蛋白位于这些成分的上游。缺乏PMT1和PMT6的突变体是可行的，并显示出PMT1突变表型和对铁螯合剂乙二胺-二（邻羟基苯乙酸）的额外敏感性。在小鼠全身性感染模型中，缺乏Pmt6p显著降低了对内皮细胞的粘附性和总体毒力。结果表明，与Pmt1p相比，Pmt6p在白色念珠菌中调节更窄的蛋白质亚类，包括负责形态发生和抗真菌敏感性的分泌蛋白。
Protein mannosyltransferases (Pmt proteins) initiate O glycosylation of secreted proteins in fungi. We have characterized PMT6, which encodes the second Pmt protein of the fungal pathogen Candida albicans, The residues of Pmt6p are 21 and 42% identical to those of C. albicans Pmt1p and S. cerevisiae Pmt6p, respectively. Mutants lacking one or two PMT6 alleles grow normally and contain normal Pmt enzymatic activities in cell extracts but show phenotypes including a partial block of hyphal formation (dimorphism) and a supersensitivity to hygromycin B. The morphogenetic defect can be suppressed by overproduction of known components of signaling pathways, including Cek1p, Cph1p, Tpk2p, and Efg1p, suggesting a specific Pmt6p target protein upstream of these components. Mutants lacking both PMT1 and PMT6 are viable and show pmt1 mutant phenotypes and an additional sensitivity to the iron chelator ethylenediamine-di(o-hydroxyphenylacetic acid). The lack of Pmt6p significantly reduces adherence to endothelial cells and overall virulence in a mouse model of systemic infection. The results suggest that Pmt6p regulates a more narrow subclass of proteins in C. albicans than Pmt1p, including secreted proteins responsible for morphogenesis and antifungal sensitivities.