J Bacteriol. 1998 Jun;180(12):3031-8. doi: 10.1128/JB.180.12.3031-3038.1998.

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

Journal of bacteriology

H F Tsai, Y C Chang, R G Washburn, M H Wheeler, K J Kwon-Chung

PMID: 9620950 PMCID: PMC107801 DOI: 10.1128/JB.180.12.3031-3038.1998
Free PMC Article

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 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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Substances

• Complement C3
• DNA, Fungal
• Melanins
• Multienzyme Complexes
• Naphthols
• 1,8-dihydroxynaphthalene

MeSH terms

• Amino Acid Sequence
• Aspergillus fumigatus / genetics
• Aspergillus fumigatus / growth & development
• Aspergillus fumigatus / pathogenicity
• Base Sequence
• Cloning, Molecular
• Complement C3 / metabolism
• DNA, Fungal / genetics
• Gene Expression Regulation, Developmental
• Gene Expression Regulation, Fungal
• Genes, Fungal*
• Humans
• In Vitro Techniques
• Melanins / biosynthesis
• Microscopy, Electron, Scanning
• Molecular Sequence Data
• Multienzyme Complexes / genetics
• Multienzyme Complexes / metabolism
• Naphthols / metabolism
• Neutrophils / immunology
• Phagocytosis
• Phenotype
• Pigmentation / genetics
• Pigmentation / physiology
• Sequence Homology, Amino Acid
• Virulence / genetics

Publication Types

• Journal Article
• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.

Grant support

• AI-01036/AI/NIAID NIH HHS/United States

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