Understanding Aspergillus fumigatus galactosaminogalactan biosynthesis: A few questions remain

Half a century after their discovery, polymers of N-acetylgalactosamine produced by the Aspergilli have garnered new interest as mediators of fungal virulence. Recent work has focused on the Aspergillus fumigatus secreted and cell wall-associated heteropolymer, galactosaminogalactan (GAG). This polymer, composed of galactose (Gal) and partially deacetylated N-acetylgalactosamine (GalNAc), plays a role in a variety of pathogenic processes including biofilm formation, immune modulation and evasion, and resistance to antifungals. Given its many potential contributions to fungal pathogenesis, GAG is a promising therapeutic target for novel antifungal strategies. As such, several studies have sought to elucidate the biosynthetic pathways required for GAG production and secretion. Herein we review the progress made in the understanding of the molecular mechanisms underlying GAG synthesis and identify several gaps in our understanding of this process.