Analysis of the molecular interplay between Streptococcus pyogenes and its human host

Research output: ThesisDoctoral Thesis (compilation)

Abstract

The common human pathogen Streptococcus pyogenes is the causative agent of numerous mild and severe clinical conditions. It expresses a number of secreted or cell wall-anchored proteins that modulate the human immune system and facilitate colonization and spread of the pathogen in the human host.

During S. pyogenes infections, human plasma leaks into the site of infection as a consequence of inflammation. This thesis shows that S. pyogenes rapidly alters its expression of extracellular and intracellular proteins in response to human plasma. In addition, the pathogen also expresses multiple variants of its important virulence factors, M1 protein and C5a peptidase, when exposed to plasma. The function of modified M1 protein and C5a peptidase is not yet elucidated but is suggested to have important implications for the pathogenicity of S. pyogenes.

Opsonizing IgG recognizes and mediates the elimination of bacteria during infection. Here, the identification and characterization of a novel IgG cleaving cysteine proteinase of S. pyogenes, denoted IdeS, is described. IdeS facilitates S. pyogenes evasion of Fc-mediated phagocytosis by specifically cleaving the hinge region of IgG1, IgG2, IgG3, and IgG4. Moreover, data suggesting that neutrophil proteinases release immunogenic epitopes from IdeS are presented. This is a novel mechanism by which S. pyogenes exploits the human immune system and prevents its virulence factors from being eliminated by opsonizing immunoglobulins.

Details

Authors
  • Björn Johansson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Infectious Medicine

Keywords

  • Microbiology, bacteriology, virology, mycology, Biomedicinska vetenskaper (allmänt), Regulation, General biomedical sciences, IdeS, Enzyme, Virulence factors, Virulence, Bacteria, Streptococci, bakteriologi, virologi, mykologi, GAS, Protein, Mikrobiologi
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2006 May 19
Publisher
  • Department of Clinical Sciences, Lund University
Print ISBNs91-85481-98-X
Publication statusPublished - 2006
Publication categoryResearch

Bibliographic note

Defence details Date: 2006-05-19 Time: 09:15 Place: GK-salen, Biomedicinskt Centrum, Sölvegatan 19, Lund External reviewer(s) Name: Norrby-Teglund, Anna Title: Docent Affiliation: Institution of Medicin, KI, Stockholm, Sweden ---

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