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 x 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.
Alcantara
R B
RB
Veterans Affairs Medical Center, Omaha, Nebraska, USA.
Preheim
L C
LC
Gentry
M J
MJ
D000818:Animals; D016470:Bacteremia / Q000276:immunology* / Q000382:microbiology; D001426:Bacterial Proteins; D003167:Complement Activation / Q000276:immunology*; D003603:Cytotoxins / Q000235:genetics / Q000276:immunology*; D005798:Genes, Bacterial; D007700:Kinetics; D008106:Liver Cirrhosis, Experimental / Q000276:immunology* / Q000382:microbiology; D008297:Male; D010957:Plasmids; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013301:Streptolysins / Q000235:genetics / Q000276:immunology*
D001426:Bacterial Proteins; D003603:Cytotoxins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae