RESUMO
Galactosaminogalactan (GAG) is an extracellular polysaccharide produced by the mycelium of the opportunistic human fungal pathogen Aspergillus fumigatus GAG is the first polysaccharide described as a virulence factor in medical mycology. This review presents our current knowledge of the structural organization and biosynthesis of this polymer. The function of this molecule as an adhesin that also masks Aspergillus PAMPs and the impact of GAG on the modulation of the host immune response by inducing neutropenia and blocking the IL-1 signaling pathway also will be emphasised.
Assuntos
Aspergillus fumigatus/metabolismo , Biopolímeros/metabolismo , Polissacarídeos/metabolismo , Animais , Aspergilose/microbiologia , Aspergillus fumigatus/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , HumanosRESUMO
The human opportunistic pathogen Aspergillus fumigatus is recognized for its versatile cell wall when it comes to remodeling its components in adaptation to external threats, and this remodeling renders it refractory to antifungals targeting cell wall biosynthesis. A specific role for general sugar metabolism in the regulation of the synthesis of cell wall polymers has been previously demonstrated. Delving deeper into central sugar metabolism may reveal unexpected fundamental aspects in cell wall construction, as shown by the work of Zhou and coworkers (Y. Zhou, K. Yan, Q. Qin, O.G. Raimi, et al., mBio 13:e01426-22, 2022, https://doi.org/10.1128/mbio.01426-22) on the roles of the phosphoglucose isomerase of A. fumigatus in cell wall biosynthesis.
Assuntos
Aspergillus fumigatus , Parede Celular , Proteínas Fúngicas , Açúcares , Antifúngicos/metabolismo , Aspergillus fumigatus/metabolismo , Parede Celular/metabolismo , Proteínas Fúngicas/metabolismo , Glucose-6-Fosfato Isomerase/metabolismo , Polímeros/metabolismo , Açúcares/metabolismo , VirulênciaRESUMO
Galactomannan is a characteristic polysaccharide of the human filamentous fungal pathogen Aspergillus fumigatus that can be used to diagnose invasive aspergillosis. In this study, we report the isolation of a galactomannan fraction associated to membrane preparations from A. fumigatus mycelium by a lipid anchor. Specific chemical and enzymatic degradations and mass spectrometry analysis showed that the lipid anchor is a glycosylphosphatidylinositol (GPI). The lipid part is an inositol phosphoceramide containing mainly C18-phytosphingosine and monohydroxylated lignoceric acid (2OH-C(24:0) fatty acid). GPI glycan is a tetramannose structure linked to a glucosamine residue: Manalpha1-2Manalpha1-2Manalpha1-6Manalpha1-4GlcN. The galactomannan polymer is linked to the GPI structure through the mannan chain. The GPI structure is a type 1, closely related to the one previously described for the GPI-anchored proteins of A. fumigatus. This is the first time that a fungal polysaccharide is shown to be GPI-anchored.