Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans
Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans
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DOI：
10.1073/pnas.95.13.7670
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发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Gow, NAR
中科院分区：
文献类型：
--
作者：
Buurman, ET;Westwater, C;Gow, NAR
迫切需要在白色念珠菌等机会性致病真菌中鉴定新的抗真菌靶标。过去，工作重点是合成几丁质和葡聚糖，它们赋予细胞指甲机械强度和刚性。本文描述了 CaMNT1 的分子分析，CaMNT1 是一种参与甘露糖蛋白合成的基因，甘露糖蛋白是细胞壁中发现的第三大类大分子。 CaMNT1 编码 α-1,2-甘露糖基转移酶，该酶在三甘露糖寡糖结构中添加第二个甘露糖残基，该结构代表白色念珠菌中的 O-连接甘露聚糖。推导的氨基酸序列表明 CaMnt1p 是位于内侧高尔基体隔室中的 II 型膜蛋白。CaMnt1p 的缺失降低了白色念珠菌细胞彼此粘附到人类颊上皮的能力细胞和大鼠阴道上皮细胞。白色念珠菌的杂合和纯合 Camnt1 无效突变体在豚鼠和系统性念珠菌病小鼠模型中均表现出毒力的强烈减弱，在豚鼠中，这可能归因于到达和/或粘附内脏器官的能力下降。因此，正确的 CaMnt1p 介导的蛋白质 O 连接甘露糖基化对于白色念珠菌的粘附和毒力至关重要。
There is an immediate need for identification of new antifungal targets in opportunistic pathogenic fungi Like Candida albicans, In the past, efforts have focused on synthesis of chitin and glucan, which confer mechanical strength and rigidity upon the cell nail. This paper describes the molecular analysis of CaMNT1, a gene involved in synthesis of mannoproteins, the third major class of macromolecule found in the cell wall. CaMNT1 encodes an alpha-1,2-mannosyl transferase, which adds the second mannose residue in a tri-mannose oligosaccharide structure which represents O-linked mannan in C. albicans, The deduced amino acid sequence suggests that CaMnt1p is a type II membrane protein residing in a medial Golgi compartment, The absence of CaMnt1p reduced the ability of C. albicans cells to adhere to each other, to human buccal epithelial cells, and to rat vaginal epithelial cells. Both heterozygous and homozygous Camnt1 null mutants of C. albicans showed strong attenuation of virulence in guinea pig and mouse models of systemic candidosis, which, in guinea pigs, could be attributed to a decreased ability to reach and/or adhere internal organs, Therefore, correct CaMnt1p-mediated O-linked mannosylation of proteins is critical for adhesion and virulence of C. albicans.