THE DEVELOPMENTALLY-REGULATED ALB1 GENE OF ASPERGILLUS-FUMIGATUS - ITS ROLE IN MODULATION OF CONIDIAL MORPHOLOGY AND VIRULENCE

Aspergillus fumigatus, an important opportunistic pathogen which commo nly affects neutropenic patients, produces conidia with a bluish-green color. We identified a gene, alb1, which is required for conidial pig mentation. The alb1 gene encodes a putative polyketide synthase, and d isruption of alb1 resulted in an albino conidial phenotype. Expression of alb1 is developmentally regulated, and the 7-kb transcript is dete cted only during the conidiation stage. The alb1 mutation was found to block 1,3,6,8-tetrahydroxynaphthalene production, indicating that alb 1 is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning e lectron 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 resulte d in a significant increase in C3 binding on conidial surfaces, and th e 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 bindin g and neutrophil-mediated phagocytosis quantitatively similar to those of the wild type. Importantly, the alb1 disruptant had a statisticall y significant loss of virulence compared to the wild-type and alb1-com plemented strains in a murine model. These results suggest that disrup tion of alb1 causes pleiotropic effects on conidial morphology and fun gal virulence.