Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence

ABSTRACT Previous work has shown that environmental and clinical isolates of Aspergillus fumigatus represent a diverse population that occupies a variety of niches, has extensive genetic diversity, and exhibits virulence heterogeneity in a number of animal models of invasive pulmonary aspergillosis...

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Autores principales:	Caitlin H. Kowalski, Sarah R. Beattie, Kevin K. Fuller, Elizabeth A. McGurk, Yi-Wei Tang, Tobias M. Hohl, Joshua J. Obar, Robert A. Cramer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0f53fc6866644524a41350af121d46a2
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spelling	oai:doaj.org-article:0f53fc6866644524a41350af121d46a22021-11-15T15:50:15ZHeterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence10.1128/mBio.01515-162150-7511https://doaj.org/article/0f53fc6866644524a41350af121d46a22016-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01515-16https://doaj.org/toc/2150-7511ABSTRACT Previous work has shown that environmental and clinical isolates of Aspergillus fumigatus represent a diverse population that occupies a variety of niches, has extensive genetic diversity, and exhibits virulence heterogeneity in a number of animal models of invasive pulmonary aspergillosis (IPA). However, mechanisms explaining differences in virulence among A. fumigatus isolates remain enigmatic. Here, we report a significant difference in virulence of two common lab strains, CEA10 and AF293, in the murine triamcinolone immunosuppression model of IPA, in which we previously identified severe low oxygen microenvironments surrounding fungal lesions. Therefore, we hypothesize that the ability to thrive within these lesions of low oxygen promotes virulence of A. fumigatus in this model. To test this hypothesis, we performed in vitro fitness and in vivo virulence analyses in the triamcinolone murine model of IPA with 14 environmental and clinical isolates of A. fumigatus. Among these isolates, we observed a strong correlation between fitness in low oxygen in vitro and virulence. In further support of our hypothesis, experimental evolution of AF293, a strain that exhibits reduced fitness in low oxygen and reduced virulence in the triamcinolone model of IPA, results in a strain (EVOL20) that has increased hypoxia fitness and a corresponding increase in virulence. Thus, the ability to thrive in low oxygen correlates with virulence of A. fumigatus isolates in the context of steroid-mediated murine immunosuppression. IMPORTANCE Aspergillus fumigatus occupies multiple environmental niches, likely contributing to the genotypic and phenotypic heterogeneity among isolates. Despite reports of virulence heterogeneity, pathogenesis studies often utilize a single strain for the identification and characterization of virulence and immunity factors. Here, we describe significant variation between A. fumigatus isolates in hypoxia fitness and virulence, highlighting the advantage of including multiple strains in future studies. We also illustrate that hypoxia fitness correlates strongly with increased virulence exclusively in the nonleukopenic murine triamcinolone immunosuppression model of IPA. Through an experimental evolution experiment, we observe that chronic hypoxia exposure results in increased virulence of A. fumigatus. We describe here the first observation of a model-specific virulence phenotype correlative with in vitro fitness in hypoxia and pave the way for identification of hypoxia-mediated mechanisms of virulence in the fungal pathogen A. fumigatus.Caitlin H. KowalskiSarah R. BeattieKevin K. FullerElizabeth A. McGurkYi-Wei TangTobias M. HohlJoshua J. ObarRobert A. CramerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 5 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Caitlin H. Kowalski Sarah R. Beattie Kevin K. Fuller Elizabeth A. McGurk Yi-Wei Tang Tobias M. Hohl Joshua J. Obar Robert A. Cramer Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence
description	ABSTRACT Previous work has shown that environmental and clinical isolates of Aspergillus fumigatus represent a diverse population that occupies a variety of niches, has extensive genetic diversity, and exhibits virulence heterogeneity in a number of animal models of invasive pulmonary aspergillosis (IPA). However, mechanisms explaining differences in virulence among A. fumigatus isolates remain enigmatic. Here, we report a significant difference in virulence of two common lab strains, CEA10 and AF293, in the murine triamcinolone immunosuppression model of IPA, in which we previously identified severe low oxygen microenvironments surrounding fungal lesions. Therefore, we hypothesize that the ability to thrive within these lesions of low oxygen promotes virulence of A. fumigatus in this model. To test this hypothesis, we performed in vitro fitness and in vivo virulence analyses in the triamcinolone murine model of IPA with 14 environmental and clinical isolates of A. fumigatus. Among these isolates, we observed a strong correlation between fitness in low oxygen in vitro and virulence. In further support of our hypothesis, experimental evolution of AF293, a strain that exhibits reduced fitness in low oxygen and reduced virulence in the triamcinolone model of IPA, results in a strain (EVOL20) that has increased hypoxia fitness and a corresponding increase in virulence. Thus, the ability to thrive in low oxygen correlates with virulence of A. fumigatus isolates in the context of steroid-mediated murine immunosuppression. IMPORTANCE Aspergillus fumigatus occupies multiple environmental niches, likely contributing to the genotypic and phenotypic heterogeneity among isolates. Despite reports of virulence heterogeneity, pathogenesis studies often utilize a single strain for the identification and characterization of virulence and immunity factors. Here, we describe significant variation between A. fumigatus isolates in hypoxia fitness and virulence, highlighting the advantage of including multiple strains in future studies. We also illustrate that hypoxia fitness correlates strongly with increased virulence exclusively in the nonleukopenic murine triamcinolone immunosuppression model of IPA. Through an experimental evolution experiment, we observe that chronic hypoxia exposure results in increased virulence of A. fumigatus. We describe here the first observation of a model-specific virulence phenotype correlative with in vitro fitness in hypoxia and pave the way for identification of hypoxia-mediated mechanisms of virulence in the fungal pathogen A. fumigatus.
format	article
author	Caitlin H. Kowalski Sarah R. Beattie Kevin K. Fuller Elizabeth A. McGurk Yi-Wei Tang Tobias M. Hohl Joshua J. Obar Robert A. Cramer
author_facet	Caitlin H. Kowalski Sarah R. Beattie Kevin K. Fuller Elizabeth A. McGurk Yi-Wei Tang Tobias M. Hohl Joshua J. Obar Robert A. Cramer
author_sort	Caitlin H. Kowalski
title	Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence
title_short	Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence
title_full	Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence
title_fullStr	Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence
title_full_unstemmed	Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence
title_sort	heterogeneity among isolates reveals that fitness in low oxygen correlates with <named-content content-type="genus-species">aspergillus fumigatus</named-content> virulence
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/0f53fc6866644524a41350af121d46a2
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Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Virulence

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