Galactofuranose attenuates cellular adhesion ofAspergillus fumigatus

Abstract

SummaryGalactofuranose (Galf) is a major molecule found in cell wall polysaccharides, secreted glycoproteins, membrane lipophosphoglycans and sphingolipids of Aspergillus fumigatus. The initial step in the Galf synthetic pathway is the re-arrangement of UDP-galactopyranose to UDP-Galf through the action of UDP-galactopyranose mutase. A mutant lacking the AfUGM1 gene encoding the UDPgalactopyranose mutase has been constructed. In the mutant, though there is a moderate reduction in the mycelial growth associated with an increased branching, it remains as pathogenic and as resistant to cell wall inhibitors and phagocytes as the wild-type parental strain. The major phenotype seen is a modification of the cell wall surface that results in an increase in adhesion of the mutants to different inert surfaces (glass and plastic) and epithelial respiratory cells. The adhesive phenotype is due to the unmasking of the mannan consecutive to the removal of galactofuran by the ugm1 mutation. Removal of the mannan layer from the mutant surface by a mannosidase treatment abolishes mycelial adhesion to surfaces.

Overlapping and Distinct Roles of Aspergillus fumigatus UDP-glucose 4-Epimerases in Galactose Metabolism and the Synthesis of Galactose-containing Cell Wall Polysaccharides

“…These data are consistent with those from mutations in other components of the galactomannan biosynthetic pathways. For example, deletion of ugm1 in A. fumigatus resulted not only in an absence of galactomannan but also an increase in galactosaminogalactan synthesis and biofilm adherence (6). Although galactosaminogalactan production has not been studied in A. nidulans, it was reported that the deletion of ugmA and ugeA was associated with an increase in adherence (55), suggesting a similar phenomenon may also occur in this organism.…”

“…latory controls at various levels of gene expression and protein synthesis of other pathway components. Although a deficiency in galactosaminogalactan is not lethal, it renders the strain nonadherent, which is not the case for galactomannan deficiency (5,6,8,12,22). Thus, in the absence of a specific requirement for galactomannan, it is possible that the fungus preferentially diverts its resources to preserve galactosaminogalactan synthesis for adherence to surfaces or biofilm homeostasis.…”

“…Galf residues are also found in a variety of other fungal glycoproteins and glycolipids (6,7). Although the role of galactomannan, and Galf, in virulence remains unclear (6,8), immunodetection of Galf antigen by EB-A2 antibody is a widely used diagnostic test for invasive aspergillosis (9 -11). Galactomannan biosynthesis has been best studied in the nonpathogenic species Aspergillus nidulans.…”

Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans

“…In Leishmania, loss of Galf synthesis or of the key galactofuranosyltransferase required to synthesize surface lipophosphoglycan results in severe defects in survival both in the insect and in the early stages of mammalian infection (15)(16)(17)(18). In the pathogenic fungus Aspergillus fumigatus, the presence of Galf in secreted glycoproteins, glycolipids, and cell wall polysaccharides (7,8) improves cell integrity (19 -21) and reduces adhe-sion to mammalian epithelial and endothelial surfaces by shielding underlying mannan structures (20). Galf may also play a role in immune recognition of pathogenic microbes.…”

Biofilm Exopolysaccharides of Pathogenic Fungi: Lessons from Bacteria

“…Galactomannan, which consists of a mannan core decorated with ␤-1,5-linked galactofuranose, is dispensable for biofilm formation, and galactofuranose-deficient mutants exhibit increased biofilm formation as a consequence of increased production of GAG (8,10,16). ␣-Glucans are abundant within the biofilm matrix; however, the role of this polysaccharide in biofilm formation has not been studied (13,(17)(18)(19).…”