Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains

ABSTRACT Fungi are versatile organisms which thrive in hostile environments, including the International Space Station (ISS). Several isolates of the human pathogen Aspergillus fumigatus have been found contaminating the ISS, an environment with increased exposure to UV radiation. Secondary metaboli...

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Autores principales:	Adriana Blachowicz, Nicholas Raffa, Jin Woo Bok, Tsokyi Choera, Benjamin Knox, Fang Yun Lim, Anna Huttenlocher, Clay C. C. Wang, Kasthuri Venkateswaran, Nancy P. Keller
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Aspergillus fumigatus space station UV-C melanin secondary metabolite spore Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9bfacf0135244b58ba42cb7021097440
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spelling	oai:doaj.org-article:9bfacf0135244b58ba42cb70210974402021-11-15T15:56:57ZContributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains10.1128/mBio.03415-192150-7511https://doaj.org/article/9bfacf0135244b58ba42cb70210974402020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03415-19https://doaj.org/toc/2150-7511ABSTRACT Fungi are versatile organisms which thrive in hostile environments, including the International Space Station (ISS). Several isolates of the human pathogen Aspergillus fumigatus have been found contaminating the ISS, an environment with increased exposure to UV radiation. Secondary metabolites (SMs) in spores, such as melanins, have been shown to protect spores from UV radiation in other fungi. To test the hypothesis that melanin and other known spore SMs provide UV protection to A. fumigatus isolates, we subjected SM spore mutants to UV-C radiation. We found that 1,8-dihydroxynaphthalene (DHN)-melanin mutants of two clinical A. fumigatus strains (Af293 and CEA17) but not an ISS-isolated strain (IF1SW-F4) were more sensitive to UV-C than their respective wild-type (WT) strains. Because DHN-melanin has been shown to shield A. fumigatus from the host immune system, we examined all DHN mutants for virulence in the zebrafish model of invasive aspergillosis. Following recent studies highlighting the pathogenic variability of different A. fumigatus isolates, we found DHN-melanin to be a virulence factor in CEA17 and IF1SW-F4 but not Af293. Three additional spore metabolites were examined in Af293, where fumiquinazoline also showed UV-C-protective properties, but two other spore metabolites, monomethylsulochrin and fumigaclavine, provided no UV-C-protective properties. Virulence tests of these three SM spore mutants indicated a slight increase in virulence of the monomethylsulochrin deletion strain. Taken together, this work suggests differential roles of specific spore metabolites across Aspergillus isolates and by types of environmental stress. IMPORTANCE Fungal spores contain secondary metabolites that can protect them from a multitude of abiotic and biotic stresses. Conidia (asexual spores) of the human pathogen Aspergillus fumigatus synthesize several metabolites, including melanin, which has been reported to be important for virulence in this species and to be protective against UV radiation in other fungi. Here, we investigate the role of melanin in diverse isolates of A. fumigatus and find variability in its ability to protect spores from UV-C radiation or impact virulence in a zebrafish model of invasive aspergillosis in two clinical strains and one ISS strain. Further, we assess the role of other spore metabolites in a clinical strain of A. fumigatus and identify fumiquinazoline as an additional UV-C-protective molecule but not a virulence determinant. The results show differential roles of secondary metabolites in spore protection dependent on the environmental stress and strain of A. fumigatus. As protection from elevated levels of radiation is of paramount importance for future human outer space explorations, the discovery of small molecules with radiation-protective potential may result in developing novel safety measures for astronauts.Adriana BlachowiczNicholas RaffaJin Woo BokTsokyi ChoeraBenjamin KnoxFang Yun LimAnna HuttenlocherClay C. C. WangKasthuri VenkateswaranNancy P. KellerAmerican Society for MicrobiologyarticleAspergillus fumigatusspace stationUV-Cmelaninsecondary metabolitesporeMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus space station UV-C melanin secondary metabolite spore Microbiology QR1-502
spellingShingle	Aspergillus fumigatus space station UV-C melanin secondary metabolite spore Microbiology QR1-502 Adriana Blachowicz Nicholas Raffa Jin Woo Bok Tsokyi Choera Benjamin Knox Fang Yun Lim Anna Huttenlocher Clay C. C. Wang Kasthuri Venkateswaran Nancy P. Keller Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains
description	ABSTRACT Fungi are versatile organisms which thrive in hostile environments, including the International Space Station (ISS). Several isolates of the human pathogen Aspergillus fumigatus have been found contaminating the ISS, an environment with increased exposure to UV radiation. Secondary metabolites (SMs) in spores, such as melanins, have been shown to protect spores from UV radiation in other fungi. To test the hypothesis that melanin and other known spore SMs provide UV protection to A. fumigatus isolates, we subjected SM spore mutants to UV-C radiation. We found that 1,8-dihydroxynaphthalene (DHN)-melanin mutants of two clinical A. fumigatus strains (Af293 and CEA17) but not an ISS-isolated strain (IF1SW-F4) were more sensitive to UV-C than their respective wild-type (WT) strains. Because DHN-melanin has been shown to shield A. fumigatus from the host immune system, we examined all DHN mutants for virulence in the zebrafish model of invasive aspergillosis. Following recent studies highlighting the pathogenic variability of different A. fumigatus isolates, we found DHN-melanin to be a virulence factor in CEA17 and IF1SW-F4 but not Af293. Three additional spore metabolites were examined in Af293, where fumiquinazoline also showed UV-C-protective properties, but two other spore metabolites, monomethylsulochrin and fumigaclavine, provided no UV-C-protective properties. Virulence tests of these three SM spore mutants indicated a slight increase in virulence of the monomethylsulochrin deletion strain. Taken together, this work suggests differential roles of specific spore metabolites across Aspergillus isolates and by types of environmental stress. IMPORTANCE Fungal spores contain secondary metabolites that can protect them from a multitude of abiotic and biotic stresses. Conidia (asexual spores) of the human pathogen Aspergillus fumigatus synthesize several metabolites, including melanin, which has been reported to be important for virulence in this species and to be protective against UV radiation in other fungi. Here, we investigate the role of melanin in diverse isolates of A. fumigatus and find variability in its ability to protect spores from UV-C radiation or impact virulence in a zebrafish model of invasive aspergillosis in two clinical strains and one ISS strain. Further, we assess the role of other spore metabolites in a clinical strain of A. fumigatus and identify fumiquinazoline as an additional UV-C-protective molecule but not a virulence determinant. The results show differential roles of secondary metabolites in spore protection dependent on the environmental stress and strain of A. fumigatus. As protection from elevated levels of radiation is of paramount importance for future human outer space explorations, the discovery of small molecules with radiation-protective potential may result in developing novel safety measures for astronauts.
format	article
author	Adriana Blachowicz Nicholas Raffa Jin Woo Bok Tsokyi Choera Benjamin Knox Fang Yun Lim Anna Huttenlocher Clay C. C. Wang Kasthuri Venkateswaran Nancy P. Keller
author_facet	Adriana Blachowicz Nicholas Raffa Jin Woo Bok Tsokyi Choera Benjamin Knox Fang Yun Lim Anna Huttenlocher Clay C. C. Wang Kasthuri Venkateswaran Nancy P. Keller
author_sort	Adriana Blachowicz
title	Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains
title_short	Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains
title_full	Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains
title_fullStr	Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains
title_full_unstemmed	Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains
title_sort	contributions of spore secondary metabolites to uv-c protection and virulence vary in different <named-content content-type="genus-species">aspergillus fumigatus</named-content> strains
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/9bfacf0135244b58ba42cb7021097440
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Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Strains

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