Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation.

Pinzan CF, Valero C, de Castro PA, da Silva JL, Earle K, Liu H, Horta MAC, Kniemeyer O, Krüger T, Pschibul A, Cömert DN, Heinekamp T, Brakhage AA, Steenwyk JL, Mead ME, Hermsdorf N, Filler SG, da Rosa-Garzon NG, Delbaje E, Bromley MJ, Cabral H, Diehl C, Angeli CB, Palmisano G, Ibrahim AS, Rinker DC, Sauters TJC, Steffen K, Gumilang A, Rokas A, Gago S, Dos Reis TF, Goldman GH (2024) Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation. Nat Microbiol 9(10), 2710-2726.

Abstract

Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1β, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection.

Leibniz-HKI-Authors

Axel A. Brakhage
Derya Nur Coemert
Thorsten Heinekamp
Olaf Kniemeyer
Thomas Krüger
Annica Pschibul

Identifier

doi: 10.1038/s41564-024-01782-y

PMID: 39191887