Background: Immunity to infections caused by Streptococcus pneumoniae is dependent on complement. There are wide
variations in sensitivity to complement between S. pneumoniae strains that could affect their ability to cause invasive
infections. Although capsular serotype is one important factor causing differences in complement resistance between
strains, there is also considerable other genetic variation between S. pneumoniae strains that may affect complementmediated
immunity. We have therefore investigated whether genetically distinct S. pneumoniae strains with the same
capsular serotype vary in their sensitivity to complement mediated immunity.
Methodology and Principal Findings: C3b/iC3b deposition and neutrophil association were measured using flow
cytometry assays for S. pneumoniae strains with different genetic backgrounds for each of eight capsular serotypes. For
some capsular serotypes there was marked variation in C3b/iC3b deposition between different strains that was
independent of capsule thickness and correlated closely to susceptibility to neutrophil association. C3b/iC3b deposition
results also correlated weakly with the degree of IgG binding to each strain. However, the binding of C1q (the first
component of the classical pathway) correlated more closely with C3b/iC3b deposition, and large differences remained in
complement sensitivity between strains with the same capsular serotype in sera in which IgG had been cleaved with IdeS.
Conclusions: These data demonstrate that bacterial factors independent of the capsule and recognition by IgG have strong
effects on the susceptibility of S. pneumoniae to complement, and could therefore potentially account for some of the
differences in virulence between strains.