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Title: EFFECT OF ALB1 GENE OF ASPERGILLUS FUMIGATUS ON OPSONOPHAGOCYTOSIS

Author
item WASHBURN, R
item TSAI, H
item CHANG, Y
item Wheeler, Michael - Mike
item KWON-CHUNG, K

Submitted to: American Society for Microbiology
Publication Type: Proceedings
Publication Acceptance Date: 5/17/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Aspergillus fumigatus is an opportunistic mold that causes invasive infection chiefly in individuals with neutropenia or impaired neutrophil function. Complement-mediated opsonization and phagocytic killing are believed to contribute to host defenses against Aspergillus, but opsonization of resting bluish-green wild-type conidia is know to be inefficient. Bluish-green pigment synthesis is likely to interfere with alternative complement pathway-mediated opsonization, given our earlier report of quantitatively lower **125 I-labeled complement component C3 binding to a bluish-green wild-type strain vs. reddish-pink and albino mutants. A. fumigatus produces bluish-green pigment via the dihydroxynaphthalene (DHN)-melanin pathway. We recently identified a developmentally-regulated gene, alb1, that was expressed only during conidiation and encoded a putative polyketide synthase. Disruption of alb1 1resulted in an albino phenotype with significantly reduced virulence in mice, as well as enhanced alternative complement pathway-mediated opsonization and neutrophil-mediated phagocytosis compared to wild-type A. fumigatus and an alb1-complemented strain. Thus, these findings suggest that one mechanism by which bluish-green pigment synthesis contributes to virulence is interference with normal opsonophagocytic clearance mechanisms.