Human Complement Factor H Binds to Outer Membrane Protein Rck of Salmonella

Serum resistance, or resistance to complement-mediated killing, is a key virulence property of microbial pathogens. Rck is a 17-kDa outer membrane protein encoded on the virulence plasmid of Salmonella enterica serovars Typhimurium and Enteritidis. When expressed in either Escherichia coli or S. enterica Typhimurium, Rck confers serum resistance independent of LPS length. Recently, the Rck homolog from Yersinia enterocolitica, Ail, has been shown to bind the complement regulatory protein factor H (fH). Based on these observations, we hypothesized that Rck may also possess this ability. Using both flow cytometery and direct binding analysis, we demonstrate that Rck expressed in E. coli binds fH. We observed fH binding to Rck from human serum and also using the purified protein. Expression of Rck protected bacteria from alternative pathway-mediated killing and was associated with a reduction in C3b, Bb, and membrane attack complex deposition. fH bound to Rck promoted C3b cleavage in the presence of factor I. Binding was specific and mediated by two regions in fH, the short consensus repeats 5-7 and 19 to 20. These results suggest that fH recruitment by Rck is functional and can protect a normally serum-sensitive heterologous host against complement attack. Binding and exploitation of fH may thus contribute to Rck-mediated serum resistance. The Journal of Immunology, 2010, 185: 1763-1769.