title: Antibody orientation at bacterial surfaces is related to invasive infection.
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.
authors.affiliation: Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden. pontus.nordenfelt@childrens.harvard.edu
authors.forename: Pontus
authors.initials: P
authors.lastname: Nordenfelt
authors.forename: Sofia
authors.initials: S
authors.lastname: Waldemarson
authors.forename: Adam
authors.initials: A
authors.lastname: Linder
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Christofer
authors.initials: C
authors.lastname: Karlsson
authors.forename: Johan
authors.initials: J
authors.lastname: Malmström
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000097:blood / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001934:Branchial Region / Q000276:immunology / Q000382:microbiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism; D019115:Fasciitis, Necrotizing / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification / Q000235:genetics / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis; D017386:Sequence Homology, Amino Acid; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D013290:Streptococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity* / Q000648:ultrastructure
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; C014689:streptococcal M protein; D003165:Complement System Proteins