The Staphylococcus aureus polysaccharide capsule and Efb-dependent fibrinogen shield act in concert to protect against phagocytosis

Microbiology (Reading). 2016 Jul;162(7):1185-1194. doi: 10.1099/mic.0.000293. Epub 2016 Apr 25.

Abstract

Staphylococcus aureus has developed many mechanisms to escape from human immune responses. To resist phagocytic clearance, S. aureus expresses a polysaccharide capsule, which effectively masks the bacterial surface and surface-associated proteins, such as opsonins, from recognition by phagocytic cells. Additionally, secretion of the extracellular fibrinogen binding protein (Efb) potently blocks phagocytic uptake of the pathogen. Efb creates a fibrinogen shield surrounding the bacteria by simultaneously binding complement C3b and fibrinogen at the bacterial surface. By means of neutrophil phagocytosis assays with fluorescently labelled encapsulated serotype 5 (CP5) and serotype 8 (CP8) strains we compare the immune-modulating function of these shielding mechanisms. The data indicate that, in highly encapsulated S. aureus strains, the polysaccharide capsule is able to prevent phagocytic uptake at plasma concentrations <10 %, but loses its protective ability at higher concentrations of plasma. Interestingly, Efb shows a strong inhibitory effect on both capsule-negative and encapsulated strains at all tested plasma concentrations. Furthermore, the results suggest that both shielding mechanisms can exist simultaneously and collaborate to provide optimal protection against phagocytosis at a broad range of plasma concentrations. As opsonizing antibodies will be shielded from recognition by either mechanism, incorporating both capsular polysaccharides and Efb in future vaccines could be of great importance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Bacterial / immunology
  • Bacterial Capsules / metabolism*
  • Bacterial Proteins / metabolism*
  • Complement C3b / metabolism
  • Fibrinogen / metabolism*
  • Fluorescent Dyes
  • Humans
  • Immunomodulation / immunology
  • Microscopy, Confocal
  • Neutrophils / immunology*
  • Opsonin Proteins / metabolism
  • Phagocytosis / immunology*
  • Polysaccharides, Bacterial / metabolism*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / metabolism

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • Efb protein, Staphylococcus aureus
  • Fluorescent Dyes
  • Opsonin Proteins
  • Polysaccharides, Bacterial
  • Complement C3b
  • Fibrinogen