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Antibody orientation at bacterial surfaces is related to invasive infection.

Nordenfelt, Pontus LU ; Waldemarson, Sofia LU ; Linder, Adam LU ; Mörgelin, Matthias LU ; Karlsson, Christofer LU ; Malmström, Johan LU and Björck, Lars LU (2012) In Journal of Experimental Medicine 209(13). p.2367-2381
Abstract
Several of the most significant bacterial pathogens in humans, including Streptococcus pyogenes, express surface proteins that bind IgG antibodies via their fragment crystallizable (Fc) region, and the dogma is that this protects the bacteria against phagocytic killing in blood. However, analysis of samples from a patient with invasive S. pyogenes infection revealed dramatic differences in the presence and orientation of IgG antibodies at the surface of bacteria from different sites. In the throat, IgG was mostly bound to the bacterial surface via Fc, whereas in the blood IgG was mostly bound via fragment antigen-binding (Fab). In infected and necrotic tissue, the Fc-binding proteins were removed from the bacterial surface. Further... (More)
Several of the most significant bacterial pathogens in humans, including Streptococcus pyogenes, express surface proteins that bind IgG antibodies via their fragment crystallizable (Fc) region, and the dogma is that this protects the bacteria against phagocytic killing in blood. However, analysis of samples from a patient with invasive S. pyogenes infection revealed dramatic differences in the presence and orientation of IgG antibodies at the surface of bacteria from different sites. In the throat, IgG was mostly bound to the bacterial surface via Fc, whereas in the blood IgG was mostly bound via fragment antigen-binding (Fab). In infected and necrotic tissue, the Fc-binding proteins were removed from the bacterial surface. Further investigation showed that efficient bacterial IgGFc-binding occurs only in IgG-poor environments, such as saliva. As a consequence, the bacteria are protected against phagocytic killing, whereas in blood plasma where the concentration of IgG is high, the antibodies preferentially bind via Fab, facilitating opsonization and bacterial killing. IgG-poor environments represent the natural habitat for IgGFc-binding bacteria, and IgGFc-binding proteins may have evolved to execute their function in such environments. The lack of protection in plasma also helps to explain why cases of severe invasive infections with IgGFc-binding bacteria are so rare compared with superficial and uncomplicated infections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
209
issue
13
pages
2367 - 2381
publisher
Rockefeller University Press
external identifiers
  • WOS:000312539900005
  • PMID:23230002
  • Scopus:84871858066
ISSN
1540-9538
DOI
10.1084/jem.20120325
language
English
LU publication?
yes
id
bbe13c9c-dca7-4b5c-ab16-f4fd443a5769 (old id 3347327)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23230002?dopt=Abstract
date added to LUP
2013-01-02 15:31:45
date last changed
2016-11-20 04:23:35
@misc{bbe13c9c-dca7-4b5c-ab16-f4fd443a5769,
  abstract     = {Several of the most significant bacterial pathogens in humans, including Streptococcus pyogenes, express surface proteins that bind IgG antibodies via their fragment crystallizable (Fc) region, and the dogma is that this protects the bacteria against phagocytic killing in blood. However, analysis of samples from a patient with invasive S. pyogenes infection revealed dramatic differences in the presence and orientation of IgG antibodies at the surface of bacteria from different sites. In the throat, IgG was mostly bound to the bacterial surface via Fc, whereas in the blood IgG was mostly bound via fragment antigen-binding (Fab). In infected and necrotic tissue, the Fc-binding proteins were removed from the bacterial surface. Further investigation showed that efficient bacterial IgGFc-binding occurs only in IgG-poor environments, such as saliva. As a consequence, the bacteria are protected against phagocytic killing, whereas in blood plasma where the concentration of IgG is high, the antibodies preferentially bind via Fab, facilitating opsonization and bacterial killing. IgG-poor environments represent the natural habitat for IgGFc-binding bacteria, and IgGFc-binding proteins may have evolved to execute their function in such environments. The lack of protection in plasma also helps to explain why cases of severe invasive infections with IgGFc-binding bacteria are so rare compared with superficial and uncomplicated infections.},
  author       = {Nordenfelt, Pontus and Waldemarson, Sofia and Linder, Adam and Mörgelin, Matthias and Karlsson, Christofer and Malmström, Johan and Björck, Lars},
  issn         = {1540-9538},
  language     = {eng},
  number       = {13},
  pages        = {2367--2381},
  publisher    = {ARRAY(0x8229c40)},
  series       = {Journal of Experimental Medicine},
  title        = {Antibody orientation at bacterial surfaces is related to invasive infection.},
  url          = {http://dx.doi.org/10.1084/jem.20120325},
  volume       = {209},
  year         = {2012},
}