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Infection and Immunity, June 1999, p. 2862-2866, Vol. 67, No. 6
0019-9567/99/$04.00+0

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

Rosemarie B. Alcantara,1,2 Laurel C. Preheim,1,2,3 and Martha J. Gentry1,2,3,*

Veterans Affairs Medical Center,1 Creighton University School of Medicine,2 and University of Nebraska College of Medicine,3 Omaha, Nebraska

Received 28 December 1998/Returned for modification 27 January 1999/Accepted 15 March 1999

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 × 107 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.

* Corresponding author. Mailing address: Research Service (151), V.A. Medical Center, 4101 Woolworth Ave., Omaha, NE 68105. Phone: (402) 346-8800 ext. 3033. Fax: (402) 449-0604. E-mail: mgentry{at}creighton.edu.

Infection and Immunity, June 1999, p. 2862-2866, Vol. 67, No. 6
0019-9567/99/$04.00+0


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