Giuseppe
Emeritus
[Source: The Journal of Experimental Medicine, full text: (LINK). Abstract, edited.]
Published December 10, 2012 // <CITE><ABBR>JEM</ABBR> vol. 209 no. 13 2367-2381 / </CITE>The Rockefeller University Press, doi: 10.1084/jem.20120325 / ? 2012 Nordenfelt et al.
Article
Antibody orientation at bacterial surfaces is related to invasive infection
Pontus Nordenfelt 1,2, Sofia Waldemarson 2, Adam Linder 1, Matthias M?rgelin 1, Christofer Karlsson 2, Johan Malmstr?m 2, and Lars Bj?rck 1
Author Affiliations: <SUP>1</SUP>Department of Clinical Sciences, Faculty of Medicine; and <SUP>2</SUP>Department of Immunotechnology, Faculty of Engineering, Lund University, Lund, Sweden
CORRESPONDENCE Pontus Nordenfelt: pontus.nordenfelt@childrens.harvard.edu OR Lars Bj?rck: lars.bjorck@med.lu.se
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.
Article
Antibody orientation at bacterial surfaces is related to invasive infection
Pontus Nordenfelt 1,2, Sofia Waldemarson 2, Adam Linder 1, Matthias M?rgelin 1, Christofer Karlsson 2, Johan Malmstr?m 2, and Lars Bj?rck 1
Author Affiliations: <SUP>1</SUP>Department of Clinical Sciences, Faculty of Medicine; and <SUP>2</SUP>Department of Immunotechnology, Faculty of Engineering, Lund University, Lund, Sweden
CORRESPONDENCE Pontus Nordenfelt: pontus.nordenfelt@childrens.harvard.edu OR Lars Bj?rck: lars.bjorck@med.lu.se
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.
- Submitted: 10 February 2012
- Accepted: 5 November 2012