The developmentally regulated alb1 gene of Aspergillus fumigatus:: Its role in modulation of conidial morphology and virulence
The developmentally regulated alb1 gene of Aspergillus fumigatus:: Its role in modulation of conidial morphology and virulence
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DOI：
10.1128/jb.180.12.3031-3038.1998
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发表时间：
1998-06-01
影响因子：
3.2
通讯作者：
Kwon-Chung, KJ
中科院分区：
文献类型：
--
作者：
Tsai, HF;Chang, YC;Kwon-Chung, KJ
烟曲霉是一种重要的机会致病菌，通常影响贫血患者，产生蓝绿色的分生孢子。我们确定了一个基因，白蛋白1，这是分生孢子色素沉着所需的。alb 1基因编码一个假定的聚酮合酶，和破坏alb 1导致在一个白化病分生孢子表型。alb 1的表达是发育调节，和7-kb的转录只在分生孢子阶段检测。发现alb 1突变阻断1，3，6，8-四羟基萘的产生，表明alb 1参与二羟基萘-黑色素的生物合成。扫描电子显微镜研究表明，白蛋白1破坏剂表现出光滑的分生孢子表面，而白蛋白1缺失的互补恢复棘状野生型表面。破坏的白蛋白1导致C3结合分生孢子表面上的显着增加，和分生孢子的白蛋白1破坏剂被人类嗜中性粒细胞以更高的速度比那些野生型摄入。产生蓝绿色分生孢子的白蛋白1补充菌株表现出低效的C3结合和嗜中性粒细胞介导的吞噬作用定量类似于野生型。重要的是，在小鼠模型中，与野生型和alb 1补充菌株相比，alb 1破坏剂具有统计学显著的毒力损失。这些结果表明，白蛋白1的破坏导致多效性的影响分生孢子形态和真菌的毒力。
Aspergillus fumigatus, an important opportunistic pathogen which commonly affects neutropenic patients, produces conidia with a bluish-green color. We identified a gene, alb1, which is required for conidial pigmentation. The alb1 gene encodes a putative polyketide synthase, and disruption of alb1 resulted in an albino conidial phenotype. Expression of alb1 is developmentally regulated, and the 7-kb transcript is detected only during the conidiation stage. The alb1 mutation was found to block 1,3,6,8-tetrahydroxynaphthalene production, indicating that alb1 is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning electron microscopy studies showed that the alb1 disruptant exhibited a smooth conidial surface, whereas complementation of the alb1 deletion restored the echinulate wild-type surface. Disruption of alb1 resulted in a significant increase in C3 binding on conidial surfaces, and the conidia of the alb1 disruptant were ingested by human neutrophils at a higher rate than were those of the wild type. The alb1-complemented strain producing bluish-green conidia exhibited inefficient C3 binding and neutrophil-mediated phagocytosis quantitatively similar to those of the wild type. Importantly, the alb1 disruptant had a statistically significant loss of virulence compared to the wild-type and alb1-complemented strains in a murine model. These results suggest that disruption of alb1 causes pleiotropic effects on conidial morphology and fungal virulence.