An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>

ABSTRACT Regulation of fungal cell wall biosynthesis is critical to maintain cell wall integrity in dynamic fungal infection microenvironments. Genes involved in this response that impact fungal fitness and host immune responses remain to be fully defined. In this study, we observed that a yeast ssd...

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Autores principales:	Arsa Thammahong, Sourabh Dhingra, Katherine M. Bultman, Joshua D. Kerkaert, Robert A. Cramer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Aspergillus fumigatus cell wall chitin pathogenesis trehalose virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/74dcdc5f93b44ab982463475e32f51af
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spelling	oai:doaj.org-article:74dcdc5f93b44ab982463475e32f51af2021-11-15T15:22:20ZAn Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>10.1128/mSphere.00244-192379-5042https://doaj.org/article/74dcdc5f93b44ab982463475e32f51af2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00244-19https://doaj.org/toc/2379-5042ABSTRACT Regulation of fungal cell wall biosynthesis is critical to maintain cell wall integrity in dynamic fungal infection microenvironments. Genes involved in this response that impact fungal fitness and host immune responses remain to be fully defined. In this study, we observed that a yeast ssd1 homolog, ssdA, in the filamentous fungus Aspergillus fumigatus is involved in trehalose and cell wall homeostasis. An ssdA null mutant strain exhibited an increase in trehalose levels and a reduction in fungal colony growth rate. In contrast, overexpression of ssdA perturbed trehalose biosynthesis and reduced germination of conidia. The ssdA null mutant strain was more resistant to cell wall-perturbing agents, while overexpression of ssdA increased sensitivity. Overexpression of ssdA significantly increased chitin levels, and both loss and overexpression of ssdA altered subcellular localization of the class V chitin synthase CsmA. Strikingly, overexpression of ssdA abolished adherence to abiotic surfaces and severely attenuated the virulence of A. fumigatus in a murine model of invasive pulmonary aspergillosis. Despite the severe in vitro fitness defects observed upon loss of ssdA, neither surface adherence nor murine survival was impacted. In conclusion, A. fumigatus SsdA plays a critical role in cell wall homeostasis impacting A. fumigatus-host interactions. IMPORTANCE The incidence of life-threatening infections caused by the filamentous fungus Aspergillus fumigatus is increasing along with an increase in the number of fungal strains resistant to contemporary antifungal therapies. The fungal cell wall and the associated carbohydrates required for its synthesis and maintenance are attractive drug targets given that many genes encoding proteins involved in cell wall biosynthesis and integrity are absent in humans. Importantly, genes and associated cell wall biosynthesis and homeostasis regulatory pathways remain to be fully defined in A. fumigatus. In this report, we identify SsdA as an important component of trehalose and fungal cell wall biosynthesis in A. fumigatus that consequently impacts the host immune response and fungal virulence in animal models of infection.Arsa ThammahongSourabh DhingraKatherine M. BultmanJoshua D. KerkaertRobert A. CramerAmerican Society for MicrobiologyarticleAspergillus fumigatuscell wallchitinpathogenesistrehalosevirulenceMicrobiologyQR1-502ENmSphere, Vol 4, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus cell wall chitin pathogenesis trehalose virulence Microbiology QR1-502
spellingShingle	Aspergillus fumigatus cell wall chitin pathogenesis trehalose virulence Microbiology QR1-502 Arsa Thammahong Sourabh Dhingra Katherine M. Bultman Joshua D. Kerkaert Robert A. Cramer An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
description	ABSTRACT Regulation of fungal cell wall biosynthesis is critical to maintain cell wall integrity in dynamic fungal infection microenvironments. Genes involved in this response that impact fungal fitness and host immune responses remain to be fully defined. In this study, we observed that a yeast ssd1 homolog, ssdA, in the filamentous fungus Aspergillus fumigatus is involved in trehalose and cell wall homeostasis. An ssdA null mutant strain exhibited an increase in trehalose levels and a reduction in fungal colony growth rate. In contrast, overexpression of ssdA perturbed trehalose biosynthesis and reduced germination of conidia. The ssdA null mutant strain was more resistant to cell wall-perturbing agents, while overexpression of ssdA increased sensitivity. Overexpression of ssdA significantly increased chitin levels, and both loss and overexpression of ssdA altered subcellular localization of the class V chitin synthase CsmA. Strikingly, overexpression of ssdA abolished adherence to abiotic surfaces and severely attenuated the virulence of A. fumigatus in a murine model of invasive pulmonary aspergillosis. Despite the severe in vitro fitness defects observed upon loss of ssdA, neither surface adherence nor murine survival was impacted. In conclusion, A. fumigatus SsdA plays a critical role in cell wall homeostasis impacting A. fumigatus-host interactions. IMPORTANCE The incidence of life-threatening infections caused by the filamentous fungus Aspergillus fumigatus is increasing along with an increase in the number of fungal strains resistant to contemporary antifungal therapies. The fungal cell wall and the associated carbohydrates required for its synthesis and maintenance are attractive drug targets given that many genes encoding proteins involved in cell wall biosynthesis and integrity are absent in humans. Importantly, genes and associated cell wall biosynthesis and homeostasis regulatory pathways remain to be fully defined in A. fumigatus. In this report, we identify SsdA as an important component of trehalose and fungal cell wall biosynthesis in A. fumigatus that consequently impacts the host immune response and fungal virulence in animal models of infection.
format	article
author	Arsa Thammahong Sourabh Dhingra Katherine M. Bultman Joshua D. Kerkaert Robert A. Cramer
author_facet	Arsa Thammahong Sourabh Dhingra Katherine M. Bultman Joshua D. Kerkaert Robert A. Cramer
author_sort	Arsa Thammahong
title	An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_short	An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_full	An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_fullStr	An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_full_unstemmed	An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_sort	ssd1 homolog impacts trehalose and chitin biosynthesis and contributes to virulence in <named-content content-type="genus-species">aspergillus fumigatus</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/74dcdc5f93b44ab982463475e32f51af
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An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>

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