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.
Highlights
The galactomannan (GM) that is produced by the human fungal pathogen Aspergillus fumigatus is an emblematic biomarker in medical mycology
Taking together all the data on the GM structure, GM that is produced by A. fumigatus is a unique fungal polysaccharide having three different forms: membrane bound through a GPI-anchor, cell wall localized GM where it is covalently linked to β-1,3-glucans and released in the culture medium as a free polymer (Figure 1)
This pathway required (1) the synthesis of nucleotide-sugar that occurs in the cytosol and their specific transport into the lumen of the Golgi, (2) the polymerisation of the mannan chain on a lipid acceptor, probably an IPC, and the addition of galactofuranose side chain, (3) the trafficking of the lipo-GM to the external face of the plasma membrane, and (4) the translocation onto the cell wall β-1,3-glucans where Dfgp play a key role
Summary
The galactomannan (GM) that is produced by the human fungal pathogen Aspergillus fumigatus is an emblematic biomarker in medical mycology. A. fumigatus is the Aspergillus species most frequently involved in human disease in developed countries. In the 1970s, the galactomannan polymer was identified as a circulating molecule in the biological fluids of immunocompromised patients that were infected with Aspergillus [2,3]. The identification of rat monoclonal antibodies against the GM has led to the development of a sensitive diagnositic enzyme immunoassay [4]. Has led to the recent development of new monoclonal antibodies and the lateral flow assay (LFA)-GM technology [7,8]. The GM polymer was described more than 50 years ago, the biological functions and biochemical pathway that are responsible for its biosynthesis remain insufficiently understood. This review highlights the last data on the GM produced by A. fumigatus and shows that the GM play an essential role for fungal apical growth and host-pathogen interactions
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