H(2)O(2)-nonproducing Streptococcus pyogenes strains: survival in stationary phase and virulence in chronic granulomatous disease

Abstract

The production of hydrogen peroxide (H(2)O(2)) 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 H(2)O(2) 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 H(2)O(2)-nonproducing strains tested in this study belonged to T type 3 or T type 12. The accumulation of H(2)O(2) started when the culture reached the late exponential phase. A rapid loss of cell viability accompanied H(2)O(2) accumulation but was completely prevented by the addition of a catalase, indicating that the lethality was actually caused by H(2)O(2). Cells of H(2)O(2)-nonproducing strains were resistant to killing by phagocytes from patients with chronic granulomatous disease (CGD), whereas those of H(2)O(2)-producing strains were subject to killing. Subcutaneous inoculation of 10(5) c.f.u. H(2)O(2)-nonproducing S. pyogenes strains into the hind footpads of CGD mice provoked more prominent swelling of the footpad than did H(2)O(2)-producing strains. The mortality rate in the CGD mice infected with the H(2)O(2)-nonproducing strains was higher than that produced by the H(2)O(2)-producing strains. It is suggested that H(2)O(2)-nonproducing S. pyogenes strains are prevalent in humans and that they may be a potential threat to the health of CGD patients.