A study was made of the variation occurring in group A streptococci during the natural course of infection in man. From 54 patients with 56 different group A streptococcal infections of the upper respiratory tract, 251 strains of streptococci, isolated at weekly intervals following infection, were tested for their capacity to resist the bacteriostatic action of normal human blood. In 52 of the infections the streptococci were of recognized serological types and were also tested for variation in their ability to produce the type-specific M protein antigen. Strains isolated in the 1st week of infection were uniformly highly resistant to bacteriostasis and elaborated large amounts of M substance. In 42 per cent of the 52 infections, strains isolated in the convalescent and carrier stages showed an increasing susceptibility to bacteriostasis correlated with a progressive loss of M substance; whereas in the remaining 58 per cent resistance to bacteriostasis and the capacity to produce M protein were maintained throughout the observation period.

In 3 different infections, the streptococci became so degraded that no M protein could be demonstrated in acid extracts of these variants. Concomitantly these strains became highly susceptible to bacteriostasis. Spontaneous reversion did not occur, but serial mouse passage reestablished these functions. These degraded variants had the same T antigen as their respective original strains.

No evidence was obtained that variation of group A streptococci in resistance to bacteriostasis or in the ability to produce the type-specific M antigen was associated (a) with the appearance of type-specific bacteriostatic antibodies; (b) with any particular serological type of streptococcus; (c) with the production of streptococcal proteinase which digests the M protein; (d) with the therapeutic administration of sulfadiazine; or (e) with the development of complications.

The possible relationship of these observations to the problem of the "dangerous carrier" of group A hemolytic streptococci is discussed.

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