A phylogenetic approach to explore theAspergillus fumigatusconidial surface-associated proteome and its role in pathogenesis

Abstract

ABSTRACTAspergillus fumigatus, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores or conidia for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface ofA. fumigatus, two closely related non-pathogenic species,Aspergillus fischeriandAspergillus oerlinghausenensis, and the cryptic pathogenAspergillus lentulus. After identifying 62 proteins uniquely expressed on theA. fumigatusconidial surface, we deleted 42 genes encoding conidial proteins. We found deletion of 33 of these genes altered susceptibility to macrophage killing, penetration and damage to epithelial cells, and cytokine production. Notably, a gene that encodes glycosylasparaginase, which modulates levels of the host pro-inflammatory cytokine IL-1β, is important for infection in an immunocompetent murine model of fungal disease. These results suggest thatA. fumigatusconidial surface proteins and effectors are important for evasion and modulation of the immune response at the onset of fungal infection.