Glycobiology Advance Access published online on January 12, 2007
Glycobiology, doi:10.1093/glycob/cwl085
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Structure and role of sialic acids on the surface of Aspergillus fumigatus conidiospores
1 Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada
2 Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada
3 To whom correspondence should be addressed: Dr. Margo M. Moore, Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada phone: 604-291-3441, fax: 604-291-3496, E-mail: mmoore{at}sfu.ca
Received on October 22, 2006; revised on December 21, 2006; accepted on January 2, 2007
Aspergillus fumigatus is an opportunistic fungal pathogen that causes a life-threatening invasive fungal disease (invasive aspergillosis) in immunocompromised individuals. The first step of pathogenesis is thought to be the attachment of conidia to proteins in lung tissue. Previous studies in our laboratory have shown that conidia adhere to basal lamina proteins via negatively charged sugars on their surface, presumably sialic acids. Sialic acids are a family of greater than 50 substituted derivatives of a 9-carbon monosaccharide, neuraminic acid. The purpose of this study was twofold: 1) to determine the structure of sialic acids and the glycan acceptor on A. fumigatus oligosaccharides, and 2) to determine the effect of removing sialic acids from conidia on conidial binding to the extracellular matrix protein fibronectin, and phagocytosis of conidia by cultured macrophages and type 2 pneumocytes. Surface sialic acids were removed using Micromonospora viridifaciens sialidase or mild acid hydrolysis using acetic acid. Lectin binding studies revealed that the majority of conidial sialic acids are 
2,6-linked to a galactose residue. High-pressure liquid chromatography of derivatized sialic acids released from conidia revealed that unsubstituted N-acetylneuraminic acid is the predominant surface sialic acid. Enzymatic sialic acid removal significantly decreased the binding of conidia to fibronectin by greater than 65% when compared to sham-treated controls. In addition, removal of sialic acids decreased conidial uptake by cultured murine macrophages and Type 2 pneumocytes by 33% and 53%, respectively. Hence, sialylated molecules on A. fumigatus conidia are ligands for both professional and non-professional phagocytes.
Key words: adhesion / fibronectin / high-pressure liquid chromatography / phagocytosis / virulence factor
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