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ARS Home » Research » Publications at this Location » Publication #91447
Title: DEVELOPMENTALLY REGULATED ALB1 GENE OF ASPERGILLUS FUMIGATUS: ITS ROLE IN MODULATION OF CONIDIAL MORPHOLOGY AND VIRULENCE

Author
item TSAI, HUEI-FUNG - NIAID
item CHANG, YUN - NIAID
item WASHBURN, RONALD - WAKE FOREST UNIV MEDICAL
item Wheeler, Michael - Mike
item KWON-CHUNG, K - NIAID

Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/14/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary: The fungus Aspergillus fumigatus, an important opportunistic pathogen commonly affecting immuno-compromised patients, produces conidia with bluish-green pigment. We identified a gene called alb1, which is required for conidial pigmentation. The alb1 gene is responsible for production of an enzyme called polyketide synthase and disruption of the alb1 gene resulted in production of an albino strain of the fungus that produced white colored conidia. Disruption of the alb1 gene was found to block 1,3,6,8-tetrahydroxynaphthalene production indicating that the gene is involved in dihydroxynaphthalene melanin synthesis. Scanning electron microscopy studies showed that the albino strain exhibits a smooth conidial surface whereas repair of the gene back to normal produced a strain of the fungus identical in color to the normal strain and restored the characteristic normal surface. Conidia of the albino strain were infested by human neutropils at a higher rate than the bluish green conidia of the normal strain. Conidia of the strain with the repaired alb1 gene produced bluish green conidia that were similar to those of the normal strain in their resistance to attack by neutrophils. Importantly, the albino strain had a significant loss in virulence compared to the normal strain and the strain with the repaired gene, when the three strains were injected into mice. These results showed that damage to the alb1 gene causes related effects on conidial morphology and fungal virulence.

Technical Abstract: Aspergillus fumigatus, an important opportunistic pathogen commonly affecting neutropenic patients, produces 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 only detected during the conidiation stage. The alb1 mutation was found to block 1,3,6,8- tetrahydroxynaphathalene production indicating that alb1 is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning electron microscopy studies showed that the alb1 disruptant exhibits a smooth conidia 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 the wild type. The complemented alb1 strain producing bluish-green conidia exhibited inefficient C3 binding and neutrophil-mediated phagocytosis, quantitatively similar to wild type. Importantly, the alb1 disruptant had a statistically significant loss in virulence compared to 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.