Antibody orientation at bacterial surfaces is related to invasive infection.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3347327
- author
- Nordenfelt, Pontus LU ; Waldemarson, Sofia LU ; Linder, Adam LU ; Mörgelin, Matthias LU ; Karlsson, Christofer LU ; Malmström, Johan LU and Björck, Lars LU
- organization
- publishing date
- 2012
- 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
- pmid:23230002
- 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
- 2016-04-04 09:31:42
- date last changed
- 2023-01-05 20:13:38
@article{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 = {{Rockefeller University Press}}, series = {{Journal of Experimental Medicine}}, title = {{Antibody orientation at bacterial surfaces is related to invasive infection.}}, url = {{https://lup.lub.lu.se/search/files/5348375/3458181.pdf}}, doi = {{10.1084/jem.20120325}}, volume = {{209}}, year = {{2012}}, }