H2O2-nonproducing Streptococcus pyogenes strains:: survival in stationary phase and virulence in chronic granulomatous disease

The production of hydrogen peroxide (H2O2) and related phenotypes were studied with Streptococcus pyogenes strains isolated from cases of pharyngitis or severe group A streptococcal infections. Of the 46 strains examined (34 from severe infections and 12 from pharyngitis cases), 25 strains accumulated H2O2 in the culture medium when grown under glucose-limited, aerobic conditions, whereas the rest of the strains did not. There was no correlation between these traits and the type of disease from which each strain had been isolated. The H2O2-nonproducing strains tested in this study belonged to T type 3 or T type 12. The accumulation of H2O2 started when the culture reached the late exponential phase. A rapid loss of cell viability accompanied H2O2 accumulation but was completely prevented by the addition of a catalase, indicating that the lethality was actually caused by H2O2. Cells of H2O2-nonproducing strains were resistant to killing by phagocytes from patients with chronic granulomatous disease (CGD), whereas those of H2O2-producing strains were subject to killing. Subcutaneous inoculation of 10(5) c.f.u. H2O2-nonproducing S. pyogenes strains into the hind footpads of CGD mice provoked more prominent swelling of the footpad than did H2O2-producing strains. The mortality rate in the CGD mice infected with the H2O2-nonproducing strains was higher than that produced by the H2O2-producing strains. It is suggested that H2O2-nonproducing S. pyogenes strains are prevalent in humans and that they may be a potential threat to the health of CGD patients.