The Developmentally Regulatedalb1Gene ofAspergillus fumigatus: Its Role in Modulation of Conidial Morphology and Virulence

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Abstract
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 ofalb1 resulted in an albino conidial phenotype. Expression of alb1 is developmentally regulated, and the 7-kb transcript is detected only during the conidiation stage. Thealb1 mutation was found to block 1,3,6,8-tetrahydroxynaphthalene production, indicating thatalb1 is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning electron microscopy studies showed that thealb1 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. Thealb1-complemented strain producing bluish-green conidia exhibited inefficient C3 binding and neutrophil-mediated phagocytosis quantitatively similar to those of the wild type. Importantly, thealb1 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 ofalb1 causes pleiotropic effects on conidial morphology and fungal virulence.