Characterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>

ABSTRACT Aspergillus fischeri is closely related to Aspergillus fumigatus, the major cause of invasive mold infections. Even though A. fischeri is commonly found in diverse environments, including hospitals, it rarely causes invasive disease. Why A. fischeri causes less human disease than A. fumigat...

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Autores principales:	Matthew E. Mead, Sonja L. Knowles, Huzefa A. Raja, Sarah R. Beattie, Caitlin H. Kowalski, Jacob L. Steenwyk, Lilian P. Silva, Jessica Chiaratto, Laure N. A. Ries, Gustavo H. Goldman, Robert A. Cramer, Nicholas H. Oberlies, Antonis Rokas
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	comparative genomics evolution of virulence fungal pathogenesis laeA secondary metabolism specialized metabolism Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b33d94e13f4f4a608430a1aa3a20f95e
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id	oai:doaj.org-article:b33d94e13f4f4a608430a1aa3a20f95e
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	comparative genomics evolution of virulence fungal pathogenesis laeA secondary metabolism specialized metabolism Microbiology QR1-502
spellingShingle	comparative genomics evolution of virulence fungal pathogenesis laeA secondary metabolism specialized metabolism Microbiology QR1-502 Matthew E. Mead Sonja L. Knowles Huzefa A. Raja Sarah R. Beattie Caitlin H. Kowalski Jacob L. Steenwyk Lilian P. Silva Jessica Chiaratto Laure N. A. Ries Gustavo H. Goldman Robert A. Cramer Nicholas H. Oberlies Antonis Rokas Characterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>
description	ABSTRACT Aspergillus fischeri is closely related to Aspergillus fumigatus, the major cause of invasive mold infections. Even though A. fischeri is commonly found in diverse environments, including hospitals, it rarely causes invasive disease. Why A. fischeri causes less human disease than A. fumigatus is unclear. A comparison of A. fischeri and A. fumigatus for pathogenic, genomic, and secondary metabolic traits revealed multiple differences in pathogenesis-related phenotypes. We observed that A. fischeri NRRL 181 is less virulent than A. fumigatus strain CEA10 in multiple animal models of disease, grows slower in low-oxygen environments, and is more sensitive to oxidative stress. Strikingly, the observed differences for some traits are of the same order of magnitude as those previously reported between A. fumigatus strains. In contrast, similar to what has previously been reported, the two species exhibit high genomic similarity; ∼90% of the A. fumigatus proteome is conserved in A. fischeri, including 48/49 genes known to be involved in A. fumigatus virulence. However, only 10/33 A. fumigatus biosynthetic gene clusters (BGCs) likely involved in secondary metabolite production are conserved in A. fischeri and only 13/48 A. fischeri BGCs are conserved in A. fumigatus. Detailed chemical characterization of A. fischeri cultures grown on multiple substrates identified multiple secondary metabolites, including two new compounds and one never before isolated as a natural product. Additionally, an A. fischeri deletion mutant of laeA, a master regulator of secondary metabolism, produced fewer secondary metabolites and in lower quantities, suggesting that regulation of secondary metabolism is at least partially conserved. These results suggest that the nonpathogenic A. fischeri possesses many of the genes important for A. fumigatus pathogenicity but is divergent with respect to its ability to thrive under host-relevant conditions and its secondary metabolism. IMPORTANCE 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.
format	article
author	Matthew E. Mead Sonja L. Knowles Huzefa A. Raja Sarah R. Beattie Caitlin H. Kowalski Jacob L. Steenwyk Lilian P. Silva Jessica Chiaratto Laure N. A. Ries Gustavo H. Goldman Robert A. Cramer Nicholas H. Oberlies Antonis Rokas
author_facet	Matthew E. Mead Sonja L. Knowles Huzefa A. Raja Sarah R. Beattie Caitlin H. Kowalski Jacob L. Steenwyk Lilian P. Silva Jessica Chiaratto Laure N. A. Ries Gustavo H. Goldman Robert A. Cramer Nicholas H. Oberlies Antonis Rokas
author_sort	Matthew E. Mead
title	Characterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>
title_short	Characterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>
title_full	Characterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>
title_fullStr	Characterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>
title_full_unstemmed	Characterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>
title_sort	characterizing the pathogenic, genomic, and chemical traits of <italic toggle="yes">aspergillus fischeri</italic>, a close relative of the major human fungal pathogen <italic toggle="yes">aspergillus fumigatus</italic>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b33d94e13f4f4a608430a1aa3a20f95e
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spelling	oai:doaj.org-article:b33d94e13f4f4a608430a1aa3a20f95e2021-11-15T15:22:05ZCharacterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>10.1128/mSphere.00018-192379-5042https://doaj.org/article/b33d94e13f4f4a608430a1aa3a20f95e2019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00018-19https://doaj.org/toc/2379-5042ABSTRACT Aspergillus fischeri is closely related to Aspergillus fumigatus, the major cause of invasive mold infections. Even though A. fischeri is commonly found in diverse environments, including hospitals, it rarely causes invasive disease. Why A. fischeri causes less human disease than A. fumigatus is unclear. A comparison of A. fischeri and A. fumigatus for pathogenic, genomic, and secondary metabolic traits revealed multiple differences in pathogenesis-related phenotypes. We observed that A. fischeri NRRL 181 is less virulent than A. fumigatus strain CEA10 in multiple animal models of disease, grows slower in low-oxygen environments, and is more sensitive to oxidative stress. Strikingly, the observed differences for some traits are of the same order of magnitude as those previously reported between A. fumigatus strains. In contrast, similar to what has previously been reported, the two species exhibit high genomic similarity; ∼90% of the A. fumigatus proteome is conserved in A. fischeri, including 48/49 genes known to be involved in A. fumigatus virulence. However, only 10/33 A. fumigatus biosynthetic gene clusters (BGCs) likely involved in secondary metabolite production are conserved in A. fischeri and only 13/48 A. fischeri BGCs are conserved in A. fumigatus. Detailed chemical characterization of A. fischeri cultures grown on multiple substrates identified multiple secondary metabolites, including two new compounds and one never before isolated as a natural product. Additionally, an A. fischeri deletion mutant of laeA, a master regulator of secondary metabolism, produced fewer secondary metabolites and in lower quantities, suggesting that regulation of secondary metabolism is at least partially conserved. These results suggest that the nonpathogenic A. fischeri possesses many of the genes important for A. fumigatus pathogenicity but is divergent with respect to its ability to thrive under host-relevant conditions and its secondary metabolism. IMPORTANCE 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.Matthew E. MeadSonja L. KnowlesHuzefa A. RajaSarah R. BeattieCaitlin H. KowalskiJacob L. SteenwykLilian P. SilvaJessica ChiarattoLaure N. A. RiesGustavo H. GoldmanRobert A. CramerNicholas H. OberliesAntonis RokasAmerican Society for Microbiologyarticlecomparative genomicsevolution of virulencefungal pathogenesislaeAsecondary metabolismspecialized metabolismMicrobiologyQR1-502ENmSphere, Vol 4, Iss 1 (2019)

Characterizing the Pathogenic, Genomic, and Chemical Traits of <italic toggle="yes">Aspergillus fischeri</italic>, a Close Relative of the Major Human Fungal Pathogen <italic toggle="yes">Aspergillus fumigatus</italic>

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