Role of Pneumolysin’s Complement-Activating Activity during Pneumococcal Bacteremia in Cirrhotic Rats

We investigated the role of pneumolysin’s complement-activating activity during Streptococcus pneumoniae bacteremia in a hypocomplementemic, cirrhotic host. Isogenic mutant pneumococcal strains, in which pneumolysin was expressed from a plasmid, were used. These strains included H+C+, expressing wild-type pneumolysin with both cytolytic and complement-activating activity; PLY−, carrying the plasmid without the pneumolysin gene; and, H+C−, expressing pneumolysin with cytolytic activity only. In control rats, intravenous infection with 2.0 × 10(7) CFU of H+C+ per ml of blood resulted in a decrease in bacteremia of 3.5 log units by 18 h postinfection and 55% mortality. By contrast, cirrhotic rats infected similarly with the H+C+ strain demonstrated a 0.2-log-unit increase in bacteremia by 18 h postinfection and 100% mortality. Both control and cirrhotic rats cleared the PLY− strain more effectively from their bloodstreams by 18 h postinfection (6.2 and 5.6 log unit decreases, respectively). Infection with the PLY− strain also resulted in low mortality (0 and 14%, respectively) for control and cirrhotic rats. When infected with the H+C− strain (without complement-activating activity), both groups cleared the organism from their bloodstreams nearly as well as they did the PLY− strain. Furthermore, the mortality rate for control and cirrhotic rats was identical after infection with the H+C− strain. These studies suggest that pneumolysin production contributes to decreased pneumococcal clearance from the bloodstream and higher mortality in both control and cirrhotic rats. However, pneumolysin’s complement-activating activity may uniquely enhance pneumococcal virulence in the hypocomplementemic, cirrhotic host.