Author
WASHBURN, R - WAKE FOREST UNIV-MEDICAL | |
TSAI, H - NIH, BETHESDA, MD | |
CHANG, Y - NIH, BETHESDA, MD | |
Wheeler, Michael - Mike | |
KWON-CHUNG, K - NIH, BETHESDA, MD |
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. |