Effects of Expression of PspC on the Ability of to Evade Complement-Mediated Immunity.

and are genetically closely related and both frequently colonise the naso-oropharynx, yet is a common cause of invasive infections whereas is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of and strains to complement-mediated immunity, demonstrating strains were susceptible to complement-mediated opsonophagocytosis. resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, was unable to bind factor H. The TIGR4 strain was expressed in the SK142 strain to create a strain. Immunoblots demonstrated the strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to , reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type strain. However, in mouse models the strain remained unable to establish persistent infection. Unlike strains, culture in serum or blood did not support increased CFU of the strains. These results suggest is highly sensitive to opsonisation with complement partially due to an inability to bind Factor H, but even when complement sensitivity was reduced by expression of , poor growth in physiological fluid limited the virulence of in mice.