Galactosaminogalactan

Galactosaminogalactan (commonly abbreviated as GAG or GG), is an exopolysaccharide composed of galactose and N-acetylgalactosamine (GalNAc). It is commonly found in the biofilm and cell wall of various fungal species.^[1][2][3] Although the sugar residues are arranged in no particular/discrete order, and thus a heteroglycan, the residues are all linked by α-1,4 glycosidic bonds. Galactosaminogalactan is typically extracted by ethanol precipitation from liquid culture or by alkaline treatment from the cell wall. Once extracted, galactosaminogalactan becomes highly insoluble.

In Aspergillus fumigatus, a causative agent of aspergillosis, galactosaminogalactan is required for adherence to host tissue, to mask PAMPs like β-1,3-glucans and to mediate virulence in several animal models.^[4] While its role in pathogenesis is still being defined, galactosaminogalactan has been found in histological sections of lungs of patients with aspergillosis.^[5] Besides its role in fungal virulence, certain fractions of laboratory purified galactosaminogalactan has been shown to induce neutrophil apoptosis ^[6] and reduce inflammation. ^[7]

Synthesis

Similar to other fungal cell wall polysaccharides, galactosaminogalactan is synthesized by polymerization of nucleotide sugars. Although the actual glycosyltransferase responsible for polymerization has not been reported, the synthesis of precursor nucleotide sugars has been studied. The galactose component originates from UDP-galactose and the GalNAc component originates from UDP-N-acetylgalactosamine. These nucleotide sugars are not physiologically favored and must to be converted from UDP-glucose and Uridine diphosphate N-acetylglucosamine (GlcNAc), respectively. The UDP-glucose 4-epimerase Uge3 is responsible for these conversions.^[8]

References

1. Bardalaye, P.C., and Nordin, J.H. (1976). Galactosaminogalactan from cell walls of Aspergillus niger. J Bacteriol 125, 655-669
2. Takada, H., Arakj, Y., Ito, E. (1980). Structure of Polygalactosamine Produced by Aspergillus parasiticus. Biochem. 89, 1265-1274
3. Fontaine, T., Delangle, A., Simenel, C., Coddeville, B., van Vliet, S.J., van Kooyk, Y., Bozza, S., Moretti, S., Schwarz, F., Trichot, C., et al. (2011). Galactosaminogalactan, a new immunosuppressive polysaccharide of Aspergillus fumigatus. In PLoS Pathog, pp. e1002372
4. Gravelat, F.N., Beauvais, A., Liu, H., Lee, M.J., Snarr, B.D., Chen, D., Xu, W., Kravtsov, I., Hoareau, C.M.Q., Vanier, G., et al. (2013). Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System. In PLoS Pathog. e.1003575
5. Loussert, C., Schmitt, C., Prevost, M.C., Balloy, V., Fadel, E., Philippe, B., Kauffmann-Lacroix, C., Latge, J.P., and Beauvais, A. (2010). In vivo biofilm composition of Aspergillus fumigatus. Cell Microbiol 12, 405-410
6. Robinet, P., Baychelier, F., Fontaine, T., Picard, C., Debre, P., Vieillard, V., Latge, J.P., and Elbim, C. (2014). A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells. Journal of Immunology. 192(11):5332-42
7. Gresnigt, M.S., Bozza, S., Becker, K.L., Joosten, L.A., Abdollahi-Roodsaz, S., van der Berg, W.B., Dinarello, C.A., Netea, M.G., Fontaine, T., De Luca, A., et al. (2014). A polysaccharide virulence factor from Aspergillus fumigatus elicits anti-inflammatory effects through induction of Interleukin-1 receptor antagonist. PLoS Pathog 10, e1003936
8. Lee MJ, Gravelat FN, Cerone RP, Baptista SD, Campoli PV, Choe SI, Kravtsov I, Vinogradov E, Creuzenet C, Liu H, Berghuis AM, Latgé JP, Filler SG, Fontaine T, Sheppard DC. Overlapping and distinct roles of Aspergillus fumigatus UDP-glucose 4-epimerases in galactose metabolism and the synthesis of galactose-containing cell wall polysaccharides. J Biol Chem. 2014 Jan 17;289(3):1243-56.