A purified group A streptococcal pyrogenic exotoxin. Physiochemical and biological properties including the enhancement of susceptibility to endotoxin lethal shock

Abstract

Purified pyrogenic exotoxin from Group A streptococcal filtrates (Streptococcus pyogenes, type 10, strain NY-5) has been characterized primarily as a protein complexed with hyaluronic acid. Amino acid composition and analysis revealed a typical acidic protein with an average molecular weight of 29,000. The purified exotoxin was free of streptolysins O and S, nicotinamide adenine dinucleotidases (NADases), deoxyribonucleases (DNases), mucopeptide, and endotoxins. The biological activity was destroyed when the exotoxin was heated at 65 degrees C for 30 min or boiled for 2 min. The biological activities investigated were pyrogenicity in rabbits (minimal pyrogenic dose-3 hr, 0.07 microg/kg), lethality in rabbits (LD(50), 3500 microg/kg), skin test dose in human skin (> 10(9) skin test doses, per mg toxin), cytotoxicity of rabbit spleen macrophage (Cytotoxic Index 0.5-10 microg/ml), enhancement of susceptibility to endotoxin shock (in rabbits > 100,000-fold), and antigenic analysis (A-type toxin). The exotoxin was immunogenic and it was possible, therefore, to immunize animals against the various toxic activities. The immunity was specific for the A-type toxin. The clinical implications of the highly significant enhancement effect of these exotoxins are discussed. It is suggested that clinical or subclinical infection with Group A streptococci could prepare the host for fatal shock from Gram-negative infections or the inadvertent injection of small amounts of Gram-negative bacterial endotoxins.