PROTECTIVE EFFECT OF HYALURONIDASE AND TYPE-SPECIFIC ANTI-M SERUM ON EXPERIMENTAL GROUP A STREPTOCOCCUS INFECTIONS IN MICE

Abstract

Five strains of encapsulated group A streptococci of different serol. types, each with a glossy and a matt variant, were studied to compare the roles of the M substance and the hyaluronic acid capsule in virulence of these microorganisms. As criteria of virulence, 2 different and distinct systems were employed (1) an in vitro test involving the capacity of the streptococcal cells to resist phagocytosis by leukocytes in human blood; and (2) an in vivo test involving the ability of group A streptococci to kill mice following intraperit. inoculation. The protective effect of anti-M serum and an enzyme, hyaluronidase, which hydrolyzes the capsular material, was also studied in the in vivo system against group A streptococcal infections in mice. On the basis of the evidence presented, it appears that the hyaluronic acid capsule is one of the factors influencing virulence of group A streptococci, but that the M antigen appears to be a far more important factor in determining this property. Encapsulated variants, both glossy and matt, were slightly less susceptible to phagocytosis than those from which the capsule had been removed with hyaluronidase. Glossy variants, containing no M substance, were readily phagocyted; matt, M-containing variants were resistant to phagocytosis except in the presence of anti-M serum when they became fully susceptible. Only the M-containing, matt strains were mouse-virulent. Mice were protected against infections with these strains: (a) By removal of the capsule with hyaluronidase, which resulted in slight protection, but only against 10 M.L.D. Early and intensive treatment was required to produce this effect; i.e., simultaneous injn. of enzyme and streptococci followed by prolonged enzyme therapy, (b) By a single injn. of nati-M serum admd. the day before inoculation of the streptococci, which resulted in protection against 100,000 M. L. D. (c) By combined use of enzyme and anti-M serum, an additive effect of the 2 protective agents occurred, which resulted in protection against 1,000,000 M. L. D.