The fungal cell wall comprises different carbohydrates either as part of glycoconjugates, like glycolipids and glycoproteins, or as constituents of its core structure. During infection the cell wall of pathogenic fungi has to be robust enough to withstand the stress applied by the host immune response. Moreover, distinct cell wall carbohydrates are likely to be recognized by host pattern recognition receptors, a key event in the innate immune response to fungal infections. We currently analyze a set of mannosyltransferases of the pathogenic mold Aspergillus fumigatus that by homology to their Saccharomyces counterparts are supposed to catalyze key steps in the formation of glycoconjugates. GDP-mannose:inositol-phosphorylceramide (MIPC)-derived glycosphingolipids are important pathogen-associated molecular patterns (PAMP) of Candida albicans and have recently been discussed as relevant PAMPs of A. fumigatus. We identified MitA as the only MIPC transferase in A. fumigatus. A 916;mitA mutant lacks MIPC and MIPC-derived glycosphingolipids and accumulates the precursor IPC. The mutant grows normally, shows no defects in cell wall or membrane organization and a normal resistance to various stressors. However, it is delayed in germination and sensitive to high Ca2+ concentrations. The 916;mitA mutant is not significantly impaired in its virulence or ability to trigger a cytokine response in macrophages, arguing against a role of MIPC-derived glycosphingolipids as important A. fumigatus PAMPs. We have also analyzed two mutants that lack key enzymes in the synthesis of O- and N-linked glycans, namely Mnt1 and OchA. Data on their fitness, pathogenicity and interaction with innate immune cells will be presented.
Full conference title:
10th EUROPEAN CONFERENCE ON FUNGAL GENETICS
- ECFG 10th (2010)