A phylogenetic approach to explore the Aspergillus fumigatus conidial surface-associated proteome and its role in pathogenesis.

Abstract

Aspergillus 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 of A. fumigatus , two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis , and the cryptic pathogen Aspergillus lentulus . After identifying 62 proteins uniquely expressed on the A. fumigatus conidial 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 that A. fumigatus conidial surface proteins and effectors are important for evasion and modulation of the immune response at the onset of fungal infection.

• Authors: Clara Valero, Camila Figueiredo Pinzan, Patrícia Alves de Castro, Norman van Rhijn, Kayleigh Earle, Hong Liu, Maria Augusta Crivelente Horta, Olaf Kniemeyer, Thomas Krüger, Annica Pschibul, Derya Nur Coemert, Thorsten Heinekamp, Axel A Brakhage, Jacob L Steenwyk, Matthew E Mead, Antonis Rokas, Scott G Filler, Nathalia Gonsales da Rosa-Garzon, Hamilton Cabral, Endrews Deljabe, Michael J Bromley, Claudia B Angeli, Giuseppe Palmisano, Ashraf S Ibrahim, Sara Gago, Thaila F Dos Reis, Gustavo H Goldman
• Journal: bioRxiv : the preprint server for biology (bioRxiv) (Aug 22 2023) United States
• PMID: 37662192 (Publication Type: Preprint)