Pneumolysin-induced complement depletion during experimental pneumococcal bacteremia

To quantify complement depletion by pneumolysin during Streptococcus pneumo niae bacteremia, cirrhotic and control rats were infected intravenously wit h one of three isogenic mutant strains of S. pneumoniae expressing differen t forms of pneumolysin. Outcome measures included clearance of the organism s from the bloodstream, alterations in 50% serum hemolytic complement (CH50 ) activity and complement C3 levels during infection, and serum opsonic cap acity at 18 h postinfection. Cirrhotic rats had significantly lower CH50 an d C3 levels than control rats, both before and after infection, However, in itial complement levels did not predict bacterial load after 18 h of infect ion, Changes in CH50 and C3 levels over the 18-h period correlated with num bers of H+C+ but not H+C- or PLY- organisms in the bloodstream at 18 h post infection, The sera of cirrhotic rats infected with the H+C+ strain had sig nificantly decreased levels of C3 and showed significantly lower opsonizing activity for S. pneumoniae than sera from H+C+-infected control rats. Thes e studies suggest that under limiting concentrations of complement, the exp ression of pneumolysin by pneumococci has a significant, negative effect on serum complement levels and reduces serum opsonic activity.