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

Author:

Goldman Gustavo1ORCID,Valero Clara2,Pinzan Camila1,de Castro Patrícia3,Rhijn Norman van4ORCID,Earle Kayleigh5,Liu Hong6,Horta Maria Augusta7,Kniemeyer Olaf8ORCID,Kruger Thomas9ORCID,Pschibul Annica10,Coemert Derya10,Heinekamp Thorsten10ORCID,Brakhage Axel11ORCID,Steenwyk Jacob12,Mead Matthew12,Rokas Antonis12ORCID,Filler Scott13,Rosa-Garzon Nathalia da7,Delbaje Endrews14ORCID,Bromley Michael4ORCID,Angeli Claudia15ORCID,Palmisano Giuseppe16,Ibrahim Ashraf17ORCID,Gago Sara4ORCID,Reis Thaila does18

Affiliation:

1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Bloco Q, Universidade de São Paulo

2. Manchester Fungal Infection Group

3. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo

4. University of Manchester

5. Manchester Fungal Infection Group, Division of Evolution, Infection, and Genomics, Faculty of Biology, Medicine and Health, University of Manchester

6. The Lundquist Institute for Biomedical Innovation

7. FCFRP, Universidade de Sao Paulo

8. Leibniz Institute for Natural Product Research and Infection Biology (HKI)

9. Hans Knoell Institute

10. Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) and Institute of Microbiology, Friedrich Schiller University

11. Leibniz Institute HKI

12. Vanderbilt University

13. Division of Infectious Diseases, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

14. University of São Paulo

15. ICB, Universidade de Sao Paulo

16. ICB-USP

17. The Lundquist Institute at Harbor-University of California Los Angeles Medical Center

18. University of Sao Paulo

Abstract

Abstract Aspergillus fumigatus, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores (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 assessed null mutants for 42 genes encoding conidial proteins. 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.

Publisher

Research Square Platform LLC

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