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

Johansson, Björn LU (2006)
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... (More)
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. (Less)
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author
supervisor
opponent
  • Docent Norrby-Teglund, Anna, Institution of Medicin, KI, Stockholm, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
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
pages
122 pages
publisher
Department of Clinical Sciences, Lund University
defense location
GK-salen, Biomedicinskt Centrum, Sölvegatan 19, Lund
defense date
2006-05-19 09:15:00
ISBN
91-85481-98-X
language
English
LU publication?
yes
additional info
B. P. Johansson, F. Levander, U. von Pawel-Rammingen, T. Berggård, L. Björck and P. James. 2005. The protein expression of Streptococcus pyogenes is significantly influenced by human plasma. J Proteome Res., vol 4 pp 2302-11.
U. von Pawel-Rammingen, B. P. Johansson and L. Björck. 2002. IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G. EMBO J., vol 21 pp 1607-15.
U. von Pawel-Rammingen, B. P. Johansson, H. Tapper and L. Björck. 2002. Streptococcus pyogenes and phagocytic killing. Nat Med., vol 8 pp 1044-5.
B. P. Johansson, L. Moritz, R. Nilsson and U. von Rawel-Rammingen. . Neutrophil serine proteinases remove immunogenic epitopes from the streptococcal IgG cleaving enzyme IdeS, without affecting the biological activity of the enzyme. (manuscript)
id
16c72542-ab0a-43c8-ad70-5f1759ad032a (old id 546698)
date added to LUP
2016-04-01 15:38:36
date last changed
2018-11-21 20:35:33
@phdthesis{16c72542-ab0a-43c8-ad70-5f1759ad032a,
  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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.}},
  author       = {{Johansson, Björn}},
  isbn         = {{91-85481-98-X}},
  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}},
  language     = {{eng}},
  publisher    = {{Department of Clinical Sciences, Lund University}},
  school       = {{Lund University}},
  title        = {{Analysis of the molecular interplay between Streptococcus pyogenes and its human host}},
  url          = {{https://lup.lub.lu.se/search/files/4438990/546699.pdf}},
  year         = {{2006}},
}