The N2N3 domains of ClfA, FnbpA and FnbpB in Staphylococcus aureus bind to human complement factor H, and their antibodies enhance the bactericidal capability of human blood

Abstract

In the complement system, the opsonin C3b binds to the bacterial cell surface and mediates the opsonophagocytosis. However, the cell-wall protein SdrE of Staphylococcus aureus inhibits the C3b activity by recruiting the complement regulatory protein factor H (fH). SdrE binds to fH via its N-terminal N2N3 domain, which are also found in six other staphylococcal cell-wall proteins. In this study, we report that not only the N2N3 domain of SdrE but also those of ClfA, FnbpA and FnbpB can bind to fH. When immobilized on a microplate, the N2N3 domains recruited fH and enhanced the factor I (fI)-mediated cleavage of C3b. When mixed with fH and S. aureus cells, the N2N3 domains inhibited the fH binding to S. aureus cells and reduced the fI-mediated C3b cleavage on the bacterial cell surface. The F(ab)′2 fragments of the rabbit N2N3 antibodies also inhibited the fH binding to the S. aureus cell surface. When added to human blood, the N2N3 antibodies or the N2N3 domain proteins significantly increased the bactericidal activity. Based on these results, we conclude that, in S. aureus, not only SdrE but also ClfA, FnbpA and FnbpB can contribute to the inhibition of C3b-mediated opsonophagocytosis.

A Factor H-Fc fusion protein increases complement-mediated opsonophagocytosis and killing of community associated methicillin-resistant Staphylococcus aureus

“…Of note, additional S. aureus surface proteins with N-terminal domains similar to SdrE may also bind FH. However, whether these regions bind CCP19-20, has not been determined [42].…”

The Role of Nanoscale Distribution of Fibronectin in the Adhesion of Staphylococcus aureus Studied by Protein Patterning and DNA-PAINT

“…Multiple mechanisms of altered interaction have been proposed from minimum ligand spacings, , minimum ligand numbers, or patch areas. ,, While there is a significant body of work investigating eukaryote interactions, to date no similar investigations have been carried out for the role of ECM protein patterns on prokaryote adhesion. Exploring and understanding the relevant length scale of distribution of Fn binding proteins at the bacterial surface and Fn availability at a biointerface will provide a molecular insight into the primary adhesion of S. aureus at the inhomogeneous surfaces of medical implants or organized ECM in host tissues. A clear challenge when studying prokaryotes comes from their small size where application of traditional wide-field and confocal fluorescence microscopes (with diffraction limited resolutions in the range 250–500 nm) to the study at subcellular dimensions becomes difficult.…”