Characterizing the Pathogenic, Genomic, and Chemical Traits of Aspergillus fischeri , a Close Relative of the Major Human Fungal Pathogen Aspergillus fumigatus

Author:

Mead Matthew E.1,Knowles Sonja L.2,Raja Huzefa A.2,Beattie Sarah R.3,Kowalski Caitlin H.3,Steenwyk Jacob L.1ORCID,Silva Lilian P.4,Chiaratto Jessica4,Ries Laure N. A.4,Goldman Gustavo H.4ORCID,Cramer Robert A.3,Oberlies Nicholas H.2,Rokas Antonis1ORCID

Affiliation:

1. Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA

2. Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USA

3. Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA

4. Faculdade de Ciencias Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil

Abstract

Aspergillus fumigatus is the primary cause of aspergillosis, a devastating ensemble of diseases associated with severe morbidity and mortality worldwide. A. fischeri is a close relative of A. fumigatus but is not generally observed to cause human disease. To gain insights into the underlying causes of this remarkable difference in pathogenicity, we compared two representative strains (one from each species) for a range of pathogenesis-relevant biological and chemical characteristics. We found that disease progression in multiple A. fischeri mouse models was slower and caused less mortality than A. fumigatus . Remarkably, the observed differences between A. fischeri and A. fumigatus strains examined here closely resembled those previously described for two commonly studied A. fumigatus strains, AF293 and CEA10. A. fischeri and A. fumigatus exhibited different growth profiles when placed in a range of stress-inducing conditions encountered during infection, such as low levels of oxygen and the presence of chemicals that induce the production of reactive oxygen species. We also found that the vast majority of A. fumigatus genes known to be involved in virulence are conserved in A. fischeri , whereas the two species differ significantly in their secondary metabolic pathways. These similarities and differences that we report here are the first step toward understanding the evolutionary origin of a major fungal pathogen.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

Burroughs Wellcome Fund

MCTI | Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação de Amparo à Pesquisa do Estado de São Paulo

HHS | NIH | National Center for Complementary and Integrative Health

Vanderbilt University

MoSTR | National Science Foundation

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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