Galactosaminogalactan (commonly abbreviated as GAG or GG), is an
exopolysaccharide
Extracellular polymeric substances (EPS) are natural polymers of high molecular weight secreted by microorganisms into their environment. EPS establish the functional and structural integrity of biofilms, and are considered the fundamental compo ...
composed of
galactose
Galactose (, ''wikt:galacto-, galacto-'' + ''wikt:-ose#Suffix 2, -ose'', ), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweetness, sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epime ...
and
N-acetylgalactosamine (GalNAc). It is commonly found in the
biofilm
A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...
and
cell wall
A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...
of various
fungal
A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the tradit ...
species. 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
A glycosidic bond or glycosidic linkage is a type of ether bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate.
A glycosidic bond is formed between the hemiacetal or hemiketal group of ...
. Galactosaminogalactan is typically extracted by
ethanol precipitation Ethanol precipitation is a method used to purify and/or concentrate RNA, DNA, and polysaccharides such as pectin and xyloglucan from aqueous solutions by adding salt and ethanol as an antisolvent.
In DNA extraction, after separating DNA from other ...
from liquid culture or by alkaline treatment from the
cell wall
A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...
. Once extracted, galactosaminogalactan becomes highly insoluble.
In ''
Aspergillus fumigatus
''Aspergillus fumigatus'' is a species of fungus in the genus ''Aspergillus'', and is one of the most common ''Aspergillus'' species to cause disease in individuals with an immunodeficiency.
''Aspergillus fumigatus'', a saprotroph widespread in ...
'', a causative agent of
aspergillosis
Aspergillosis is a fungal infection of usually the lungs, caused by the genus ''Aspergillus'', a common mold that is breathed in frequently from the air, but does not usually affect most people. It generally occurs in people with lung diseases su ...
, galactosaminogalactan is required for adherence to host tissue, to mask
PAMPs like
β-1,3-glucans and to mediate
virulence
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abili ...
in several animal models. While its role in pathogenesis is still being defined, galactosaminogalactan has been found in
histological sections of lungs of patients with aspergillosis. Besides its role in fungal virulence, certain fractions of laboratory purified galactosaminogalactan has been shown to induce
neutrophil
Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
and reduce
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
.
Synthesis
Similar to other fungal cell wall polysaccharides, galactosaminogalactan is synthesized by polymerization of nucleotide sugars. Although the actual
glycosyltransferase
Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the "glycosyl donor") to a nucleophilic gl ...
responsible for polymerization has not been reported, the synthesis of precursor nucleotide sugars has been studied. The galactose component originates from
UDP-galactose
Uridine diphosphate galactose (Uridine diphosphate, UDP-galactose) is an intermediate in the production of polysaccharides. It is important in nucleotide sugars metabolism, and is the substrate for the transferase B4GALT5.
Sugar metabolism
Urid ...
and the
GalNAc component originates from UDP-N-acetylgalactosamine. These nucleotide sugars are not physiologically favored and must to be converted from
UDP-glucose
Uridine diphosphate glucose (uracil-diphosphate glucose, UDP-glucose) is a nucleotide sugar. It is involved in glycosyltransferase reactions in metabolism.
Functions
UDP-glucose is used in nucleotide sugar metabolism as an activated form of g ...
and
Uridine diphosphate N-acetylglucosamine (GlcNAc), respectively. The
UDP-glucose 4-epimerase Uge3 is responsible for these conversions.
[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.]
References
{{Reflist
Polysaccharides
Galactose