The Staphylococcus aureus polysaccharide capsule and Efb-dependent fibrinogen shield act in concert to protect against phagocytosis.
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.
Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Annemarie
A
Kuipers
Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Daphne A C
DAC
Stapels
Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Lleroy T
LT
Weerwind
Center for Infectious and Inflammatory Disease, Institute of Bioscience and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA.
Ya-Ping
YP
Ko
Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Maartje
M
Ruyken
Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Jean C
JC
Lee
Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Kok P M
KPM
van Kessel
Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Suzan H M
SHM
Rooijakkers
D000907:Antibodies, Bacterial / Q000276:immunology; D016667:Bacterial Capsules / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005456:Fluorescent Dyes; D006801:Humans; D056747:Immunomodulation / Q000276:immunology; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C114014:Efb protein, Staphylococcus aureus; D005456:Fluorescent Dyes; D009895:Opsonin Proteins; D011135:Polysaccharides, Bacterial; D003179:Complement C3b; D005340:Fibrinogen