Studies on the role of superoxide dismutase (SOD) in the virulence of Streptococcus pneumoniae and the effects of interferon gamma on sensitivity of phagocytes to the toxin pneumolyin

The major point of the study was into how the penumococcus copes with reactive derivatives of oxygen. Superoxide dismutase is one of the enzymes that provides protection against deleterious effects of superoxide radical by conversion of superoxide to hydrogen peroxide and molecular oxygen. In this study, it was shown that S. pneumoniae contains two types of superoxide dismutase, MnSOD and FeSOD. While the level of MnSOD increased during growth in an aerobic environment, the amount of FeSOD remained unchanged. An isogenic sodA insertion-mutant strain of S. pneumoniae was constructed to study the role for the enzyme in vitro and in vivo. Aerobically the mutant strain of S. pneumoniae, designated as D39HY1, had a lower growth rate than the wild type and exhibited susceptibility to the redox active compound, paraquat. Anaerobic growth of D39HY1 was identical to the wild-type. Virulence studies showed that the median survival time of mice infected intranasally with D39HY1 was significantly longer than mice infected with the wild type pneumococcus. In contrast to the wild-type, D39HY1 did not multiply in lungs during the first 24h but thereafter grew at the same rate as the wild-type. Appearance in the bloodstream also was delayed but growth in the blood was unimpaired by the sodA mutation.;The aim of the second project was to assess whether IFN- may enhance resistance of macrophages to the deleterious effects of bacterial products. To assess this possibility, the effects of interferon gamma on sensitivity of phagocytes to the toxin pneumolysin, an important virulence determinant of S. pneumoniae, was tested by employing respiratory burst as an assay of sublytic effects. It was observed that IFN- can alter the susceptibility of cells to the lytic effect of pneumolysin. Also the respiratory burst of IFN- treated cells was insensitive to sublytic concentrations of pneumolysin.