590 STREPTOCOCCUS 



Pathogenicity and Toxin Production. 



The various species of streptococci described above inchide some of the most 

 important pathogens of man, and are responsible for many infections of economic 

 importance among animals. 



Str. pyogenes gives rise to numerous pyogenic and septicsemic infectiona in man (see 

 Chapter 67), as well as being the cause of scarlet fever (see Chapter 66). 



It is pathogenic for a number of laboratory animals, including the rabbit, the mouse 

 and the guinea-pig ; but the virulence of different strains for these animals is by no means 

 uniform, and the guinea-pig is often relatively resistant. To obtain a highly virulent 

 strain for the mouse, or for the rabbit, it is often necessary to test a large number of strains 

 of human origin, or to adapt a strain to the new host by repeated passage. When a highly 

 virulent strain has been obtained, its intravenous injection leads to a fatal septicaemia, 

 frequently associated in the rabbit with suppurative lesions in the joints, and sometimes 

 with an ulcerative endocarditis. Intraperitoneal injection is followed by a suppurative 

 peritonitis leading to a septicsemic infection ; while subcutaneous injection is followed 

 by a locahzed abscess, with or without a subsequent generahzation. With some strains, 

 so far at least as the rabbit is concerned, intradermal injection is followed by a spreading 

 erysipelatous infection of the skin, or by a more severe dermal infection leading to necrosis ; 

 and an infection of the latter type not infrequently terminates as a septicaemia. 



Str. pyogenes is of particular interest to the pathologist in that it combines the capacity 

 for tissue invasion with the production of filtrable exotoxins. 



One of these toxins, streptococcal hsemolysin, has aheady been considered. That this 

 substance is toxic in the animal body, as well as being lytic for red blood corpuscles in 

 vitro, there can be no doubt. Its minimal lethal dose is large (5-10 ml. for the rabbit), but 

 when administered intravenously in this amount it kills the animal within 24-36 hours 

 with an associated hsemoglobinuria, and with evidence of intravascular haemolysis at 

 necropsy (McLeod and McNee 1913, Channon and McLeod 1929). Weld (1934, 1935) more 

 recently described preparations of streptolysin, obtained by extracting the cocci with 

 serum, that are fatal for mice in a dose of 0-1 ml. Streptococcal haemolysin is, as we have 

 seen, thermolabile, being inactivated at 58° C. in 30 mins. As aheady noted, Todd (1934) 

 has demonstrated the presence in lytic filtrates of two haemolysins, one oxygen-sensitive, 

 but reactivable by reduction, and another which is oxygen-stable but is very sensitive to 

 heat and to acid. Both are toxic, the S type causmg death by intravascular haemolysis, 

 the O type probably causing death by some other means. Specific antibodies, having 

 protective properties and showing no cross-neutrahzation, can be prepared against each 

 type of haemolysm (Todd 19386). 



In addition to their action on red blood corpuscles, filtrates of broth cultures of Str. 

 pyogenes have a destructive action on polymorphonuclear leucocytes. This was first 

 demonstrated by van der Velde (1894) in his studies on experimental infections with 

 streptococci ; and he named the active principle leiicocidin. It was subsequently shown 

 by Neisser and Wechsberg (1900, 1901) that this action could be demonstrated in vitro, 

 since the streptococcal filtrates, in kilhng the leucocytes, deprive them of their power of 

 reducmg methylene blue. It was early noted that streptococcal leucocidin is relatively 

 thermolabile, and most authors (see Nakayama 1920, Channon and McLeod 1929) have 

 concluded that its thermolabihty is of the same order as that of streptococcal haemolysin. 

 Channon and McLeod conclude, from this and other observations, that streptococcal 

 haemolysin and leucocidin are identical ; but Nakayama regards them as different, a view 

 that is put forward more strongly by Evans (1931) and by Gay and Oram (1933), who 

 dispute the previous findings in regard to the thermolabihty of streptococcal leucocidin, 

 and state that it withstands heating at 70° C. for 30 minutes. Todd (1942) has brought 

 evidence to suggest that the leucocidm is identical with the oxygen-labile streptolysin O, 

 and that it plays no part in the determination of virulence to mice. This problem must 

 be regarded as awaiting final solution. 



