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A quantitative Streptococcus pyogenes-human protein-protein interaction map reveals localization of opsonizing antibodies

Happonen, Lotta LU ; Hauri, Simon LU ; Svensson Birkedal, Gabriel LU ; Karlsson, Christofer LU ; de Neergaard, Therese LU ; Khakzad, Hamed; Nordenfelt, Pontus LU ; Wikström, Mats; Wisniewska, Magdalena and Björck, Lars LU , et al. (2019) In Nature Communications 10(1). p.2727-2727
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
10
issue
1
pages
2727 - 2727
publisher
Nature Publishing Group
external identifiers
  • scopus:85067619339
ISSN
2041-1723
DOI
10.1038/s41467-019-10583-5
language
English
LU publication?
yes
id
134b6187-87e6-4e8d-acb6-7ae81e041294
date added to LUP
2019-06-27 01:07:27
date last changed
2019-07-30 05:04:59
@article{134b6187-87e6-4e8d-acb6-7ae81e041294,
  abstract     = {<p>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.</p>},
  author       = {Happonen, Lotta and Hauri, Simon and Svensson Birkedal, Gabriel and Karlsson, Christofer and de Neergaard, Therese and Khakzad, Hamed and Nordenfelt, Pontus and Wikström, Mats and Wisniewska, Magdalena and Björck, Lars and Malmström, Lars and Malmström, Johan},
  issn         = {2041-1723},
  language     = {eng},
  month        = {06},
  number       = {1},
  pages        = {2727--2727},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {A quantitative Streptococcus pyogenes-human protein-protein interaction map reveals localization of opsonizing antibodies},
  url          = {http://dx.doi.org/10.1038/s41467-019-10583-5},
  volume       = {10},
  year         = {2019},
}