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

Departments of Bacteriology¹ and Pediatrics², Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Department of Microbiology, Tokyo Metropolitan Research and Laboratory of Public Health, Tokyo 169-0073, Japan³
Department of Microbiology, Faculty of Dentistry, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan⁴

Author for correspondence: Mitsumasa Saito. Tel: +81 92 642 6130. Fax: +81 92 642 6133. e-mail: msaito{at}bact.med.kyushu-u.ac.jp

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 10⁵ 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.

Keywords: group A streptococci, hydrogen peroxide, CGD, gp91-phox knockout mice

Abbreviations: BHI, brain-heart infusion; CGD, chronic granulomatous disease

^a Emeritus. Present address: 4395-2 Fukuma, Fukuoka-ken 811-3213, Japan.

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