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Streptococcus pyogenes secreted enzymes interacting with the human host

Collin, Mattias LU (2001)
Abstract
<i>Streptococcus pyogenes</i> is one of the most common bacteria infecting humans. One of the factors contributing to the disease-causing properties is the secreted streptococcal cysteine proteinase, SpeB, which degrades several host proteins in connective tissue and circulation. SpeB activity depends on the transformation from an inactive precursor, zymogen, into a mature proteinase. We show that the important cell wall-anchored M protein is involved in the unfolding and maturation of SpeB. An engineered strain lacking M protein secreted the SpeB zymogen in a conformational state that did not allow the maturation to proceed normally. Furthermore, we identified genes that were regulated by environmental changes using RNA... (More)
<i>Streptococcus pyogenes</i> is one of the most common bacteria infecting humans. One of the factors contributing to the disease-causing properties is the secreted streptococcal cysteine proteinase, SpeB, which degrades several host proteins in connective tissue and circulation. SpeB activity depends on the transformation from an inactive precursor, zymogen, into a mature proteinase. We show that the important cell wall-anchored M protein is involved in the unfolding and maturation of SpeB. An engineered strain lacking M protein secreted the SpeB zymogen in a conformational state that did not allow the maturation to proceed normally. Furthermore, we identified genes that were regulated by environmental changes using RNA fingerprinting. One of the identified glucose-induced genes encodes a phosphotransferase system that could be involved in the signaling leading to down-regulation of virulence genes in response to the nutritional status. Moreover, a novel secreted endoglycosidase, EndoS, has been identified. Purified EndoS removes the glycan from native human immunoglobulin G (IgG).This glycan is known to be important for IgG effector functions such as complement activation and binding to Fc receptors on phagocytic cells. Furthermore, it was discovered that SpeB cleaves the heavy chain of IgG resulting in distinct fragments separating the antigen-binding Fab portions from the effector-triggering Fc portion. SpeB also degrades the heavy chains of IgA, IgM, IgD and IgE. Finally, it was shown that both these enzymatic activities on human IgG have functional consequences with significantly impaired antibody-mediated killing of <i>S. pyogenes</i> in an <i>ex vivo</i> model. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Professor Kehoe, Michael, Department of Microbiology, Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, United Kingdom
organization
publishing date
type
Thesis
publication status
published
subject
keywords
RNA fingerprinting, Streptococcus pyogenes, Clinical biology, immunoglobulins, Klinisk biologi, autoimmunity, endoglycosidase, cysteine proteinase, glycosylation
pages
138 pages
publisher
BMC Biomedical Centre, Lund University
defense location
Fernströmsalen, Biomedical Center, Lund University
defense date
2001-11-09 13:15
ISBN
91-628-4966-2
language
English
LU publication?
yes
id
ee2f75a6-7b0f-4d79-92a2-c53eef4d6f07 (old id 41936)
date added to LUP
2007-06-20 13:34:21
date last changed
2016-09-19 08:45:09
@misc{ee2f75a6-7b0f-4d79-92a2-c53eef4d6f07,
  abstract     = {&lt;i&gt;Streptococcus pyogenes&lt;/i&gt; is one of the most common bacteria infecting humans. One of the factors contributing to the disease-causing properties is the secreted streptococcal cysteine proteinase, SpeB, which degrades several host proteins in connective tissue and circulation. SpeB activity depends on the transformation from an inactive precursor, zymogen, into a mature proteinase. We show that the important cell wall-anchored M protein is involved in the unfolding and maturation of SpeB. An engineered strain lacking M protein secreted the SpeB zymogen in a conformational state that did not allow the maturation to proceed normally. Furthermore, we identified genes that were regulated by environmental changes using RNA fingerprinting. One of the identified glucose-induced genes encodes a phosphotransferase system that could be involved in the signaling leading to down-regulation of virulence genes in response to the nutritional status. Moreover, a novel secreted endoglycosidase, EndoS, has been identified. Purified EndoS removes the glycan from native human immunoglobulin G (IgG).This glycan is known to be important for IgG effector functions such as complement activation and binding to Fc receptors on phagocytic cells. Furthermore, it was discovered that SpeB cleaves the heavy chain of IgG resulting in distinct fragments separating the antigen-binding Fab portions from the effector-triggering Fc portion. SpeB also degrades the heavy chains of IgA, IgM, IgD and IgE. Finally, it was shown that both these enzymatic activities on human IgG have functional consequences with significantly impaired antibody-mediated killing of &lt;i&gt;S. pyogenes&lt;/i&gt; in an &lt;i&gt;ex vivo&lt;/i&gt; model.},
  author       = {Collin, Mattias},
  isbn         = {91-628-4966-2},
  keyword      = {RNA fingerprinting,Streptococcus pyogenes,Clinical biology,immunoglobulins,Klinisk biologi,autoimmunity,endoglycosidase,cysteine proteinase,glycosylation},
  language     = {eng},
  pages        = {138},
  publisher    = {ARRAY(0xa4b54d0)},
  title        = {Streptococcus pyogenes secreted enzymes interacting with the human host},
  year         = {2001},
}