A PURIFIED GROUP A STREPTOCOCCAL PYROGENIC EXOTOXIN: PHYSICOCHEMICAL AND BIOLOGICAL PROPERTIES INCLUDING THE ENHANCEMENT OF SUSCEPTIBILITY TO ENDOTOXIN LETHAL SHOCK

doi:10.1084/jem.131.3.611

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A PURIFIED GROUP A STREPTOCOCCAL PYROGENIC EXOTOXIN : PHYSICOCHEMICAL AND BIOLOGICAL PROPERTIES INCLUDING THE ENHANCEMENT OF SUSCEPTIBILITY TO ENDOTOXIN LETHAL SHOCK

Yoon Berm Kim M.D.¹ and Dennis W. Watson Ph.D.¹

¹ From the Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455

Purified pyrogenic exotoxin from Group A streptococcal filtrates(Streptococcus pyogenes, type 10, strain NY-5) has been characterizedprimarily as a protein complexed with hyaluronic acid. Aminoacid composition and analysis revealed a typical acidic proteinwith an average molecular weight of 29,000. The purified exotoxinwas free of streptolysins O and S, nicotinamide adenine dinucleotidases(NADases), deoxyribonucleases (DNases), mucopeptide, and endotoxins.The biological activity was destroyed when the exotoxin washeated at 65°C for 30 min or boiled for 2 min.

The biologicalactivities investigated were pyrogenicity in rabbits (minimalpyrogenic dose-3 hr, 0.07 µg/kg), lethality in rabbits(LD₅₀, 3500 µg/kg), skin test dose in human skin (>10⁹ skin test doses, per mg toxin), cytotoxicity of rabbit spleenmacrophage (Cytotoxic Index 0.5–10 µg/ml), enhancementof susceptibility to endotoxin shock (in rabbits > 100,000-fold),and antigenic analysis (A-type toxin).

The exotoxin was immunogenicand it was possible, therefore, to immunize animals againstthe various toxic activities. The immunity was specific forthe A-type toxin.

The clinical implications of the highly significantenhancement effect of these exotoxins are discussed. It is suggestedthat clinical or subclinical infection with Group A streptococcicould prepare the host for fatal shock from Gram-negative infectionsor the inadvertent injection of small amounts of Gram-negativebacterial endotoxins.

Submitted on August 25, 1969

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