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

Björn Johansson

Research output: ThesisDoctoral Thesis (compilation)

187 Downloads (Pure)

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.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Infection Medicine (BMC)
Supervisors/Advisors
  • Björck, Lars, Supervisor
Award date2006 May 19
Publisher
ISBN (Print)91-85481-98-X
Publication statusPublished - 2006

Bibliographical 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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<div class="article_info">B. P. Johansson, F. Levander, U. von Pawel-Rammingen, T. Berggård, L. Björck and P. James. <span class="article_issue_date">2005</span>. <span class="article_title">The protein expression of Streptococcus pyogenes is significantly influenced by human plasma.</span> <span class="journal_series_title">J Proteome Res.</span>, <span class="journal_volume">vol 4</span> <span class="journal_pages">pp 2302-11</span>.</div>
<div class="article_info">U. von Pawel-Rammingen, B. P. Johansson and L. Björck. <span class="article_issue_date">2002</span>. <span class="article_title">IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G.</span> <span class="journal_series_title">EMBO J.</span>, <span class="journal_volume">vol 21</span> <span class="journal_pages">pp 1607-15</span>.</div>
<div class="article_info">U. von Pawel-Rammingen, B. P. Johansson, H. Tapper and L. Björck. <span class="article_issue_date">2002</span>. <span class="article_title">Streptococcus pyogenes and phagocytic killing.</span> <span class="journal_series_title">Nat Med.</span>, <span class="journal_volume">vol 8</span> <span class="journal_pages">pp 1044-5</span>.</div>
<div class="article_info">B. P. Johansson, L. Moritz, R. Nilsson and U. von Rawel-Rammingen. <span class="article_issue_date"></span>. <span class="article_title">Neutrophil serine proteinases remove immunogenic epitopes from the streptococcal IgG cleaving enzyme IdeS, without affecting the biological activity of the enzyme.</span> (manuscript)</div>

Subject classification (UKÄ)

  • Infectious Medicine

Free 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

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