S8.3c Cell wall glycans as targets for the development of new antifungals

Abstract

S8.3 How the fungal cell wall glycan can modulate the immune response?, September 23, 2022, 3:00 PM - 4:30 PMBeing an extracellular organelle, the cell wall plays a crucial role in fungal life, by protecting fungal cells from a hostile environments and providing cells with mechanical strength. Exploiting the essentiality of this cell wall, available antifungal drugs target cell wall biosynthesis directly or by altering the fungal cell membrane. However, the emergence of resistance to antifungal drugs, new at risk-cohorts, and drug-drug interaction issue with antifungals demand new/alternative therapeutic strategy. In this regard, we have identified that surfactant protein-D (SP-D; a host humoral immune component) has growth inhibitory activity on Aspergillus fumigatus, a ubiquitous airborne opportunistic pathogen. SP-D, a soluble pattern recognition receptor of the collection family, targets galactosaminogalactan and galactomannan, the cell wall glycans of A. fumigatus hyphae, as the ligands. Hyphae grown in presence of SP-D show a significant decrease in the growth and are hyperbranched compared to control hyphae. SP-D treatment alters surface exposure of hyphal cell wall polysaccharides, thereby modifying hyphal immunoreactivity. SP-D pre-treatment increases the efficacy of the echinocandin and azole classes of antifungals against A. fumigatus. Interestingly, SP-D show hyphal growth inhibitory activity against multi-/pan-azole-resistant isolates of A. fumigatus. Overall, SP-D seems to target A. fumigatus cell wall glycans to execute its fungistatic activity. We are currently investigating the exact mechanism of anti-A. fumigatus activity associated with SP-D.