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A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies
A fundamental challenge in medical microbiology is to characterize the dynamic protein–protein interaction networks formed at the host–pathogen interface. Here, we generate a quantitative interaction map between the significant human pathogen, Streptococcus pyogenes, and proteins from human saliva a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588558/ https://www.ncbi.nlm.nih.gov/pubmed/31227708 http://dx.doi.org/10.1038/s41467-019-10583-5 |
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author | Happonen, Lotta Hauri, Simon Svensson Birkedal, Gabriel Karlsson, Christofer de Neergaard, Therese Khakzad, Hamed Nordenfelt, Pontus Wikström, Mats Wisniewska, Magdalena Björck, Lars Malmström, Lars Malmström, Johan |
author_facet | Happonen, Lotta Hauri, Simon Svensson Birkedal, Gabriel Karlsson, Christofer de Neergaard, Therese Khakzad, Hamed Nordenfelt, Pontus Wikström, Mats Wisniewska, Magdalena Björck, Lars Malmström, Lars Malmström, Johan |
author_sort | Happonen, Lotta |
collection | PubMed |
description | A fundamental challenge in medical microbiology is to characterize the dynamic protein–protein interaction networks formed at the host–pathogen interface. Here, we generate a quantitative interaction map between the significant human pathogen, Streptococcus pyogenes, and proteins from human saliva and plasma obtained via complementary affinity-purification and bacterial-surface centered enrichment strategies and quantitative mass spectrometry. Perturbation of the network using immunoglobulin protease cleavage, mixtures of different concentrations of saliva and plasma, and different S. pyogenes serotypes and their isogenic mutants, reveals how changing microenvironments alter the interconnectivity of the interaction map. The importance of host immunoglobulins for the interaction with human complement proteins is demonstrated and potential protective epitopes of importance for phagocytosis of S. pyogenes cells are localized. The interaction map confirms several previously described protein–protein interactions; however, it also reveals a multitude of additional interactions, with possible implications for host–pathogen interactions involving other bacterial species. |
format | Online Article Text |
id | pubmed-6588558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65885582019-06-25 A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies Happonen, Lotta Hauri, Simon Svensson Birkedal, Gabriel Karlsson, Christofer de Neergaard, Therese Khakzad, Hamed Nordenfelt, Pontus Wikström, Mats Wisniewska, Magdalena Björck, Lars Malmström, Lars Malmström, Johan Nat Commun Article A fundamental challenge in medical microbiology is to characterize the dynamic protein–protein interaction networks formed at the host–pathogen interface. Here, we generate a quantitative interaction map between the significant human pathogen, Streptococcus pyogenes, and proteins from human saliva and plasma obtained via complementary affinity-purification and bacterial-surface centered enrichment strategies and quantitative mass spectrometry. Perturbation of the network using immunoglobulin protease cleavage, mixtures of different concentrations of saliva and plasma, and different S. pyogenes serotypes and their isogenic mutants, reveals how changing microenvironments alter the interconnectivity of the interaction map. The importance of host immunoglobulins for the interaction with human complement proteins is demonstrated and potential protective epitopes of importance for phagocytosis of S. pyogenes cells are localized. The interaction map confirms several previously described protein–protein interactions; however, it also reveals a multitude of additional interactions, with possible implications for host–pathogen interactions involving other bacterial species. Nature Publishing Group UK 2019-06-21 /pmc/articles/PMC6588558/ /pubmed/31227708 http://dx.doi.org/10.1038/s41467-019-10583-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Happonen, Lotta Hauri, Simon Svensson Birkedal, Gabriel Karlsson, Christofer de Neergaard, Therese Khakzad, Hamed Nordenfelt, Pontus Wikström, Mats Wisniewska, Magdalena Björck, Lars Malmström, Lars Malmström, Johan A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies |
title | A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies |
title_full | A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies |
title_fullStr | A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies |
title_full_unstemmed | A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies |
title_short | A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies |
title_sort | quantitative streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588558/ https://www.ncbi.nlm.nih.gov/pubmed/31227708 http://dx.doi.org/10.1038/s41467-019-10583-5 |
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