Galactomannan Produced by Aspergillus fumigatus: An Update on the Structure, Biosynthesis and Biological Functions of an Emblematic Fungal Biomarker

Abstract

The galactomannan (GM) that is produced by the human fungal pathogen Aspergillus fumigatus is an emblematic biomarker in medical mycology. The GM is composed of two monosaccharides: mannose and galactofuranose. The furanic configuration of galactose residues, absent in mammals, is responsible for the antigenicity of the GM and has favoured the development of ELISA tests to diagnose aspergillosis in immunocompromised patients. The GM that is produced by A. fumigatus is a unique fungal polysaccharide containing a tetramannoside repeat unit and having three different forms: (i) membrane bound through a glycosylphosphatidylinositol (GPI)-anchor, (ii) covalently linked to β-1,3-glucans in the cell wall, or (iii) released in the culture medium as a free polymer. Recent studies have revealed the crucial role of the GM during vegetative and polarized fungal growth. This review highlights these recent data on its biosynthetic pathway and its biological functions during the saprophytic and pathogenic life of this opportunistic human fungal pathogen.

A molecular vision of fungal cell wall organization by functional genomics and solid-state NMR

“…The low amount of mannan in this Δktr mutant could originate from membrane-bound mannan 44 or from the N- or/and O- glycan moieties of the glycoproteins, which, in contrast to the cell wall GM, are untouched in the Δktr mutants 28 . Moreover, the mannan composition was different: the ratio of Mn: 1,2 Mn 1,6 of 5:1 and 1:1 in the parental strain and Δ ktr4/7 mutant, respectively (Supplementary Table 4 ), which is in agreement with biochemical data 44 , 45 . GAG was completely depleted in the Δ gt4C mutant, followed by a significant increase in β-1,3-glucan in the mobile region.…”

Two Monoclonal Antibodies That Specifically Recognize Aspergillus Cell Wall Antigens and Can Detect Circulating Antigens in Infected Mice

“…These results demonstrate that significant amounts of the antigen are produced and shed by all four Aspergillus species into the culture media, although it was not detectable in hyphae of cultured A. niger and A. terreus by immunofluorescence. Possible reasons include differing concentrations of the antigens in the hyphal wall, masking of the epitopes within the cell wall or different configurations or orientation of the epitopes in the hyphal wall following shedding into the medium [ 29 , 34 ].…”

Fungal Pathogenesis-Related Cell Wall Biogenesis, with Emphasis on the Maize Anthracnose Fungus Colletotrichum graminicola

“…The α-core-mannan chain of FTGM consists of nine to ten sets of α-1,2-mannotetraose units connected by α-1,6-linkages, to which galactofuran side chains with β-1,5- and β-1,6-linked galactofuranosyl residues are connected via β-1,2-, β-1,3-, and/or β-1,6-bonds [ 67 ]. As FTGM is covalently connected to the chitin-β-1,3-glucan network via bonds to β-1,3-glucan and, furthermore, associated with plasma membranes via glycosylphosphatidylinositol (GPI) anchors, this polymer might play an important role in cell wall cross-linking and stability [ 67 , 68 ]. Highlighting the importance of this polymer in cell wall rigidity, mutants of A. fumigatus lacking either of the two core mannosyl transferases, CmsA or CmsB, as well as double mutants grow slowly and exhibit severe hyphal swellings [ 69 ].…”