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

Abstract

Staphylococcus aureus has developed many mechanisms to escape from human immune responses. In order 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 labeled encapsulated serotype 5 (CP5) and serotype 8 (CP8) strains we now compare the immune-modulating function of these shielding mechanisms. Our 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 as well as encapsulated strains at all tested plasma concentrations. Furthermore our results suggest that both shielding mechanisms can exist simultaneously and collaborate to provide optimal protection against phagocytosis at a broad range of plasma concentrations. Since opsonizing antibodies will be shielded from recognition by either mechanism, incorporating both capsular polysaccharides and Efb in future vaccines could be of great importance.

Dendritic Cells Internalize Staphylococcus aureus More Efficiently than Staphylococcus epidermidis, but Do Not Differ in Induction of Antigen-Specific T Cell Proliferation

“…Deletion of the cap genes required for synthesis of the S. epidermidis PGA capsule, causes an increase of S. epidermidis internalization by neutrophils [12]. Other capsular polysaccharides, such as poly-N-acetyl glucosamine (PNAG) also known as polysaccharide intercellular adhesin (PIA) or capsular polysaccharides (CP)5 and CP8, may also protect staphylococci against phagocytosis [54][55][56][57][58]. Since all strains are positive for the for the (icaADBC, cap5, cap8) genes necessary for PNAG/PIA, CP5 and CP8 synthesis, it is unlikely that these capsules are the distinguishing factor in the different level of S. aureus and S. epidermidis internalization by DCs.…”

Genome Mining and Comparative Pathogenomic Analysis of An Endemic Methicillin-Resistant Staphylococcus Aureus (MRSA) Clone, ST612-CC8-t1257-SCCmec_IVd(2B), Isolated in South Africa

“…Naicker et al reported a strong biofilm formation in ST612 compared to the other clones which may have contributed to its dominance in South Africa [60]. The clone contained only one capsular serotype, cap5, which enhances microbial virulence and offers protection against phagocytic uptake (Figure 2 and Supplementary Table S5) [61]. They also harboured the highly versatile type VII secretion system encoding the eight cluster genes associated with the release of secretions that cause pathogenesis in S. aureus [62,63].…”

Aggregating resistant Staphylococcus aureus induces hypocoagulability, hyperfibrinolysis, phagocytosis, and neutrophil, monocyte, and lymphocyte binding in canine whole blood

“…Kuipers et al demonstrated that bacterial fibrin formation reduced the innate immune response by inhibiting phagocytosis . Thus, bacterial/fibrin aggregates might be too large to be phagocytized, allowing the bacteria to escape the cells of the innate immune system .…”