The Glycosylphosphatidylinositol-Anchored Superoxide Dismutase of Scedosporium apiospermum Protects the Conidia from Oxidative Stress.

Cindy Staerck,Alphonse Calenda,Patrick Vandeputte,Maxime Fleury,Yves Delneste,Sandrine Giraud,Hajar Yaakoub,Thomas Guillemette,Julie Tabiasco,Jean-Philippe Bouchara,Charlotte Godon,Amandine Gastebois

doi:10.3390/jof7070575

Abstract

Scedosporium species are common fungal pathogens in patients with cystic fibrosis (CF). To colonize the CF lungs, fungi must cope with the host immune response, especially the reactive oxygen species (ROS) released by phagocytic cells. To this aim, pathogens have developed various antioxidant systems, including superoxide dismutases (SODs) which constitute the first-line protection against oxidative stress. Interestingly, one of the S. apiospermum SOD-encoding genes (SODD gene) exhibits a glycosylphosphatidylinositol (GPI) anchor-binding site and encodes a conidial-specific surface SOD. In this study, a SODDΔ mutant was engineered from a non-homologous end joining-deficient strain (KU70Δ) of S. apiospermum. Compared to its parent strain, the double mutant KU70Δ/SODDΔ exhibited increased susceptibility to various oxidizing agents and triazole antifungals. In addition, the loss of SodD resulted in an increased intracellular killing of the conidia by M1 macrophages derived from human blood monocytes, suggesting the involvement of this superoxide dismutase in the evasion to the host defenses. Nevertheless, one cannot disregard an indirect role of the enzyme in the synthesis or assembly of the cell wall components since transmission electron microscopic analysis revealed a thickening of the inner cell wall layer of the conidia. Further studies are needed to confirm the role of this enzyme in the pathogenesis of Scedosporium infections, including the production of a recombinant protein and study of its protective effect against the infection in a mouse model of scedosporiosis.

Highlights

IntroductionScedosporium species (phylum Ascomycota, order Microascales) are environmental molds usually living as saprophytes, mainly in highly polluted soils and contaminated water [1]
Licensee MDPI, Basel, Switzerland.Scedosporium species are environmental molds usually living as saprophytes, mainly in highly polluted soils and contaminated water [1]
Conidia processed into any experiment were collected from 9-day-old cultures grown in PDA or yeast extract-peptone-dextrose (YPD containing in g/L: yeast extract, 10; peptone, 20; glucose, 20; and chloramphenicol, 0.5%) and resuspended in sterile water or saline before to be enumerating by hematocytometer counts

Summary

Introduction

Scedosporium species (phylum Ascomycota, order Microascales) are environmental molds usually living as saprophytes, mainly in highly polluted soils and contaminated water [1]. These fungi may cause a wide variety of infections in humans. Scedosporium species rank second among the filamentous fungi colonizing the airways of CF patients, after Aspergillus fumigatus, with a prevalence rate ranging from 3.1% to 11.9% [3,4,5,6,7,8,9,10] In this clinical context, these fungi are usually responsible for a chronic colonization of the airways [11,12], which has been demonstrated as a risk factor for a disseminated infection in the case of lung or heart-lung transplantation [13]

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