The puzzling construction of the conidial outer layer of Aspergillus fumigatus

The outer layers of the fungal cell wall are the first barrier facing external challenges. In theinvasive morphotype of the airborne pathogen Aspergillus fumigatus, i.e. conidia, the outer cell wall consists of α-(1,3)-glucan, melanin and proteinaceous rodlets made up by the RodA hydrophobin. The hydrophobicity of the RodA rodlets facilitates air dispersal of conidia and progression within lungs. When conidia reach the alveolae, these are phagocytosed by host cells and killed upon germination, which requires melanin and rodlets elimination to occur. The dormant condition of the conidia protects them against activation of the host killing pathways. The outer cell wall of conidia is thus essential for maintaining the viability of the fungus. To study the role of α-(1,3)-glucan, melanin, and RodA rodlets in conidia protection, multiple mutants without two or the three major components of the outer layer were constructed and analyzed. Deletions led to the exposure of new molecules on the conidial surface. Multiple gene deletions did not always lead to logical additivity of the phenotypes. Unexpected compensatory cell wall surface modifications were indeed observed, such as the synthesis of the mycelial virulence factor galactosaminogalactan, the presence of chitin and glycoproteins or specific changes in permeability. In spite of significant modifications, sensitivity to killing by phagocytic host cells of the multiple mutants involving melanin changed little compared to the sensitive parent strain lacking melanin (ΔpksP), further indicating the importance of melanin in protecting conidia against killing by monocytes.