The developmentally regulated alb1 gene of Aspergillus fumigatus:: Its role in modulation of conidial morphology and virulence

被引:267
作者
Tsai, HF
Chang, YC
Washburn, RG
Wheeler, MH
Kwon-Chung, KJ
机构
[1] NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA
[2] Wake Forest Univ, Sch Med, Dept Internal Med, Infect Dis Sect, Winston Salem, NC 27006 USA
[3] USDA ARS, Cotton Pathol Res Unit, So Crops Res Lab, College Stn, TX 77845 USA
关键词
D O I
10.1128/JB.180.12.3031-3038.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页码:3031 / 3038
页数:8
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