title: Upregulation of capsule enables Streptococcus pyogenes to evade immune recognition by antigen-specific antibodies directed to the G-related alpha2-macroglobulin-binding protein GRAB located on the bacterial surface.
abstract: One of the major problems associated with the development of a vaccine against Streptococcus pyogenes is the ability of this pathogen to escape recognition by antibodies directed against conserved surface-associated determinants and to establish infection in the setting of an acquired immune response. Identification of the mechanism(s) used by S. pyogenes to avoid recognition by antigen-specific antibodies and escape killing in blood was the focus of this study. We showed here that S. pyogenes was capable of surviving in human blood containing high levels of antibodies directed against the G-related alpha2-macroglobulin-binding protein GRAB, a highly conserved bacterial surface protein. S. pyogenes upregulated the hyaluronic acid capsule production during incubation with human blood, suggesting that the capsule may structurally minimize antibody access to protein GRAB. This hypothesis was confirmed by the ability of anti-GRAB antibodies to promote opsonophagocytosis of a capsule-deficient mutant of S. pyogenes but not of the encapsulated wild-type strain. Capsule upregulation and protection of S. pyogenes from opsonophagocytosis in the presence of anti-GRAB antibodies was also observed in a murine model of streptococcal infection. Thus, masking of surface immunogenic determinants by the hyaluronic acid capsule may constitute a novel mechanism of S. pyogenes for evasion of antigen-specific antibodies.
authors.affiliation: Department of Microbial Pathogenicity, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. katrin.dinkla@helmholtz-hzi.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Dinkla
authors.forename: Inka
authors.initials: I
authors.lastname: Sastalla
authors.forename: Antonia W
authors.initials: AW
authors.lastname: Godehardt
authors.forename: Nina
authors.initials: N
authors.lastname: Janze
authors.forename: Gursharan S
authors.initials: GS
authors.lastname: Chhatwal
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Eva
authors.initials: E
authors.lastname: Medina
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D016667:Bacterial Capsules / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D001769:Blood / Q000382:microbiology; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009895:Opsonin Proteins; D010587:Phagocytosis; D012703:Serotyping; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000145:classification / Q000378:metabolism / Q000472:pathogenicity*; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; C119608:GRAB protein, Streptococcus pyogenes; D009895:Opsonin Proteins; D000511:alpha-Macroglobulins; D006820:Hyaluronic Acid