VIRULENCE 129 



Some old samples of serum were found to have an exalted power of neutralising 

 the oxygen-labile haemolysin of Group A hsemolytic streptococci. This was traced 

 to the activity of a contaminating bacterium which had liberated from the serum a 

 lysin-neutralising substance, which was found to be cholesterol. Cholesterol suspen- 

 sions diluted one in a million were found to neutralise the lysin. (Hewitt and Todd, 

 1939.) An interesting problem, so far unexplained, is why normal serum cholesterol 

 does not neutralise the lysin since a considerable proportion in normal blood serum 

 is " free " cholesterol. Evidently normal serum-cholesterol is not free enough to 

 neutralise the lysin but requires the chemical activities of a contaminating bacterium 

 to render it capable of combining with the lysin. 



Schwachman, Hellerman and Cohen (1934) in an examination of pneumococcal 

 hsemolysin, which is also subject to reversible inactivation by oxidising agents 

 (Avery and Neill, 1924), find close analogies to the behaviour of papain and urease. 

 They conclude that substances containing a thiol group are essential to the hsemolytic 

 activity. Not only oxidising agents but also heavy metals which combine with 

 thiol groups inactivate the hsemolysin. The question is left open whether the 

 hsemolysin itself contains the essential sulphydryl group or whether another substance, 

 similar to a coenzyme, must be present with a reduced — SH group before hsemolytic 

 activity can occur. 



In the case of hsemolysis by C diphtherice (Hewitt, 1947) reduced thiol com- 

 pounds inhibit hsemolysis and oxidising conditions favour hsemolytic activity. 



STREPTOCOCCAL VIRULENCE 



Hsemolytic streptococci grown on solid media can exist in two distinct colony 

 forms — " matt " and " glossy." Glossy colonies contain a virulent organisms and 

 the matt colonies may be either virulent or a virulent. It should be mentioned 

 that with these organisms the virulence of the different variants may show over a 

 millionfold variation. The matt form can be distinguished from the glossy by the 

 possession of a specific substance which can be detected by precipitin methods 

 (Todd and Lancefield, 1928 ; Lancefield and Todd, 1928). 



Todd (1930) has shown that by cultivation under appropriate conditions, the 

 matt form may become glossy, the matt attenuated may become virulent, and the 

 matt virulent be attenuated, thus : — 



Glossy -> Matt attenuated ^ Matt virulent 

 Specific substance ... — + + 



Virulence ...... — — -f- 



When grown on the surface of solid media fully exposed to air, the matt form 

 may become glossy, and Todd (1931, 1), has found that this effect may be attributed 

 to peroxide formation. The matt variants produce more peroxide than the glossy 

 variants and the peroxide produced has a bactericidal effect. Autosterilisation 

 of the matt forms may, therefore, be effected on solid media, since the matt colonies 

 produce more peroxide which remains in their immediate vicinity, not diffusing 

 uniformly throughout the medium as in liquid media. Repeated subculture on solid 

 media results in gradual elimination of matt colonies, until the culture may consist 

 entirely of the glossy variant. With some strains of hsemolytic streptococci there 

 is another relatively rare form of slow, natural selection of glossy forms which 



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