Pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. Prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of S. pneumoniae isolated from adult patients. PspC deletion and isogenic pspC-switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD isolates than subgroup II pspC. The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion compared to subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in PspC subgroup, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition.
