Abstract

Cell wall biosynthesis and remodeling are essential for fungal growth and development. In the fungal pathogen Aspergillus fumigatus, the β(1,3)glucan is the major cell wall polysaccharide. This polymer is synthesized at the plasma membrane by a transmembrane complex, then released into the parietal space to be remodeled by enzymes, and finally incorporated into the pre-existing cell wall. In the Glycosyl-Hydrolases family 17 (GH17) of A. fumigatus, two β(1,3)glucanosyltransferases, Bgt1p and Bgt2p, have been previously characterized. Disruption of BGT1 and BGT2 did not result in a phenotype, but sequence comparison and hydrophobic cluster analysis showed that three other genes in A. fumigatus belong to the GH17 family, SCW4, SCW11, and BGT3. In constrast to Δbgt1bgt2 mutants, single and multiple deletion of SCW4, SCW11, and BGT3 showed a decrease in conidiation associated with a higher conidial mortality and an abnormal conidial shape. Moreover, mycelium was also affected with a slower growth, stronger sensitivity to cell wall disturbing agents, and altered cell wall composition. Finally, the synthetic interactions between Bgt1p, Bgt2p, and the three other members, which support a functional cooperation in cell-wall assembly, were analyzed. Our data suggest that Scw4p, Scw11p, and Bgt3p are essential for cell wall integrity and might have antagonistic and distinct functions to Bgt1p and Bgt2p.

Highlights

  • Aspergillus fumigatus is the most common airborne fungal pathogen, causing fatal invasive aspergillosis in immunocompromised patients [1]

  • Our data suggest that Scw4p, Scw11p, and Bgt3p are essential for cell wall integrity and might have antagonistic and distinct functions to Bgt1p and Bgt2p

  • Bgt2p has been identified as a GPI anchored protein

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Summary

Introduction

Aspergillus fumigatus is the most common airborne fungal pathogen, causing fatal invasive aspergillosis in immunocompromised patients [1]. One of the most important characteristics of the fungal cell is the presence of an outer and rigid layer called the cell wall, which surrounds it This biological coat is both a rigid and protective exoskeleton and a dynamic structure. In A. fumigatus, as in other pathogenic fungi, the cell wall acts as a sieve and reservoir of antigens, enzymes, and toxins that play an active role during infection. Essential for growth, it provides the organism with a resistance from the internal turgor pressure, and protects the cell from its environment (e.g., desiccation and osmotic stress) [2,3]. Because of its absence in humans and its essentiality, the fungal cell wall is a promising target for antifungal drugs and it is important to elucidate cell wall biosynthesis and organization

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