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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • Swiss Institute of Bioinformatics
  • University of Zurich
  • University of Copenhagen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
  • Infectious Medicine
Original languageEnglish
Pages (from-to)2727
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 2019 Jun 21
Publication categoryResearch
Peer-reviewedYes