Abstract
The fungal cell wall is the first point of contact between fungal pathogens and host organisms. It serves as a protective barrier against biotic and abiotic stresses and as a signal to the host that a fungal pathogen is present. The fungal cell wall is made predominantly of carbohydrates and glycoproteins, many of which serve as binding receptors for host defence molecules or activate host immune responses through interactions with membrane-bound receptors. Plant defensins are a large family of cationic antifungal peptides that protect plants against fungal disease. Binding of the plant defensin NaD1 to the fungal cell wall has been described but the specific component of the cell wall with which this interaction occurred was unknown. The effect of binding was also unclear, that is whether the plant defensin used fungal cell wall components as a recognition motif for the plant to identify potential pathogens or if the cell wall acted to protect the fungus against the defensin. Here we describe the interaction between the fungal cell wall polysaccharides chitin and β-glucan with NaD1 and other plant defensins. We discovered that the β-glucan layer protects the fungus against plant defensins and the loss of activity experienced by many cationic antifungal peptides at elevated salt concentrations is due to sequestration by fungal cell wall polysaccharides. This has limited the development of cationic antifungal peptides for the treatment of systemic fungal diseases in humans as the level of salt in serum is enough to inactivate most cationic peptides.
Highlights
Fungal pathogens are a serious threat to humanity because of their impact on food production and human and animal health
NaD1 and NaD2 were isolated from the flowers of N. alata as described in (Lay et al, 2003a). 15N labelled NaD1 was produced in Pichia pastoris as described in (Chen et al, 2006) and purified by cation-exchange chromatography and RP-HPLC as described in (Hayes et al, 2014)
The Kd s normalized for the concentration of the monosaccharide for chitin and β-glucan were 33.0 ± 11.8 mM and 25.9 ± 5 mM respectively
Summary
Fungal pathogens are a serious threat to humanity because of their impact on food production and human and animal health. Fungal infections range from superficial skin and mucosal infections to serious infections of the blood stream and internal organs (Enoch et al, 2006; Gow and Netea, 2016). Antifungals used in both agriculture and medicine are directed to specific fungal targets such as the sterol ergosterol or biosynthesis of polysaccharides in the fungal cell wall (Kathiravan et al, 2012). Occurring antifungal peptides (AFPs) are a family of molecules with novel mechanisms of action that have the potential to meet this need (van der Weerden et al, 2013)
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