Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.

The secondary metabolome provides pathogenic fungi with a plethoric and versatile panel of molecules that can be deployed during host ingress. While powerful genetic and analytical chemistry methods have been developed to identify fungal secondary metabolites (SMs), discovering the biological activi...

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Autores principales:	Erwin Berthier, Fang Yun Lim, Qing Deng, Chun-Jun Guo, Dimitrios P Kontoyiannis, Clay C C Wang, Julie Rindy, David J Beebe, Anna Huttenlocher, Nancy P Keller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8ae9616b3bbb4715a47a40d4e4c2844a
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spelling	oai:doaj.org-article:8ae9616b3bbb4715a47a40d4e4c2844a2021-11-18T06:05:47ZLow-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.1553-73661553-737410.1371/journal.ppat.1003289https://doaj.org/article/8ae9616b3bbb4715a47a40d4e4c2844a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23592999/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The secondary metabolome provides pathogenic fungi with a plethoric and versatile panel of molecules that can be deployed during host ingress. While powerful genetic and analytical chemistry methods have been developed to identify fungal secondary metabolites (SMs), discovering the biological activity of SMs remains an elusive yet critical task. Here, we describe a process for identifying the immunosuppressive properties of Aspergillus SMs developed by coupling a cost-effective microfluidic neutrophil chemotaxis assay with an in vivo zebrafish assay. The microfluidic platform allows the identification of metabolites inhibiting neutrophil recruitment with as little as several nano-grams of compound in microliters of fluid. The zebrafish assay demonstrates a simple and accessible approach for performing in vivo studies without requiring any manipulation of the fish. Using this methodology we identify the immunosuppressive properties of a fungal SM, endocrocin. We find that endocrocin is localized in Aspergillus fumigatus spores and its biosynthesis is temperature-dependent. Finally, using the Drosophila toll deficient model, we find that deletion of encA, encoding the polyketide synthase required for endocrocin production, yields a less pathogenic strain of A. fumigatus when spores are harvested from endocrocin permissive but not when harvested from endocrocin restrictive conditions. The tools developed here will open new "function-omic" avenues downstream of the metabolomics, identification, and purification phases.Erwin BerthierFang Yun LimQing DengChun-Jun GuoDimitrios P KontoyiannisClay C C WangJulie RindyDavid J BeebeAnna HuttenlocherNancy P KellerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 4, p e1003289 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Erwin Berthier Fang Yun Lim Qing Deng Chun-Jun Guo Dimitrios P Kontoyiannis Clay C C Wang Julie Rindy David J Beebe Anna Huttenlocher Nancy P Keller Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.
description	The secondary metabolome provides pathogenic fungi with a plethoric and versatile panel of molecules that can be deployed during host ingress. While powerful genetic and analytical chemistry methods have been developed to identify fungal secondary metabolites (SMs), discovering the biological activity of SMs remains an elusive yet critical task. Here, we describe a process for identifying the immunosuppressive properties of Aspergillus SMs developed by coupling a cost-effective microfluidic neutrophil chemotaxis assay with an in vivo zebrafish assay. The microfluidic platform allows the identification of metabolites inhibiting neutrophil recruitment with as little as several nano-grams of compound in microliters of fluid. The zebrafish assay demonstrates a simple and accessible approach for performing in vivo studies without requiring any manipulation of the fish. Using this methodology we identify the immunosuppressive properties of a fungal SM, endocrocin. We find that endocrocin is localized in Aspergillus fumigatus spores and its biosynthesis is temperature-dependent. Finally, using the Drosophila toll deficient model, we find that deletion of encA, encoding the polyketide synthase required for endocrocin production, yields a less pathogenic strain of A. fumigatus when spores are harvested from endocrocin permissive but not when harvested from endocrocin restrictive conditions. The tools developed here will open new "function-omic" avenues downstream of the metabolomics, identification, and purification phases.
format	article
author	Erwin Berthier Fang Yun Lim Qing Deng Chun-Jun Guo Dimitrios P Kontoyiannis Clay C C Wang Julie Rindy David J Beebe Anna Huttenlocher Nancy P Keller
author_facet	Erwin Berthier Fang Yun Lim Qing Deng Chun-Jun Guo Dimitrios P Kontoyiannis Clay C C Wang Julie Rindy David J Beebe Anna Huttenlocher Nancy P Keller
author_sort	Erwin Berthier
title	Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.
title_short	Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.
title_full	Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.
title_fullStr	Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.
title_full_unstemmed	Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.
title_sort	low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/8ae9616b3bbb4715a47a40d4e4c2844a
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Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.

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