Five strains of encapsulated group A streptococci of different serological types, each with a glossy and a matt variant, were studied to compare the rôles of the M substance and the hyaluronic acid capsule in virulence of these microorganisms. The results indicated that both contribute to the virulence of group A streptococci but that the M antigen is the more fundamental factor.

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 injection of enzyme and streptococci followed by prolonged enzyme therapy.

(b) By a single injection of anti-M serum administered 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 two protective agents occurred, which resulted in protection against 1,000,000 M.L.D.

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