868 Clostridium 



a measure of its a-toxin content, and for comparisons of the neutralizing power of a-anti- 

 toxins (for details see Nagler 1939, Oakley and VVarraek 1941, van Heyningen 1941a, 

 Crook 1942). Lecithinase production in fluid and on agar cultures of CI. zvelchii may 

 be detected by incorporating human serum or egg-yolk extract in media containing 

 a sufficiency of free calcium. Other bacteria, mainly spore-bearing bacilli, produce 

 lecithinase-like substances (Nagler 1939, Hayward 1941, Crook 1942) but with one excep- 

 tion, CI. hijermentans (Hayward 1943), none is fully neutraUzed by a-antitoxin. 



The 0-toxin has been found only in Type A filtrates. It is a strong hsemolysin, and 

 is also lethal and necrotizing. Todd (1941) has shown that it is thermolabile and oxygen- 

 labile. The activity of oxidized 9-toxin is restored by reducing agents containing sulphydryl 

 groups. This property of reversible oxidation is shared by the O -streptolysin of Str. 

 pyogenes (Chapter 24). There is also an antigenic relationship between the two substances, 

 each being to a large extent neutraUzed by antisera prejjared agamst the other (Todd 1941). 

 6-toxin may be removed from mixtures with a-toxin by adsorption on to susceptible red 

 cell stromata (van Heyningen 19416 ; see also Gale and van Heyningen 1942). 



The |S-toxin is not hsemolytic ; it is lethal to mice, producing on intravenous injection 

 a spasmodic twitching rapidly followed by death ; given intradermally in guinea-pigs 

 and rabbits it produces necrotic lesions. The y-toxin is neither necrotizing nor hsemolytic. 

 Its existence in filtrates can be proved only by its lethal activity in mice, after the other 

 toxins have been neutralized by appropriate antitoxins. The d-toxin is hsemolytic and 

 lethal and, like y-toxin, is detected after neutraMzation of other components by anti- 

 toxins. The £-toxin, which predominates in Type D filtrates, is not haemolytic, but is 

 both lethal and necrotizing. Large doses in mice produce spasmodic twitching similar 

 to those foUo\\ing injections of ^-toxin. Smaller doses, after a latent period of several 

 days, produce paralysis. The e-toxin is produced by Type D strains as a thermostable 

 relatively non-toxic substance, which is activated by trypsin and other proteolytic enzymes 

 with the formation of the thermolabile toxin (Gill 1933, Bosworth and Glover 1935). 

 In disease produced by Type D strains (see Chapter 78) the activating enzyme is apparently 

 supplied by the infected animal, though according to Turner and Rodwell (1943) in favour- 

 able conditions extracellular proteinases of the bacillus itself will activate the toxin. It 

 should be noted that culture filtrates of Type A strains may also contain large amounts 

 of a hyaluronidase (McClean 1936 ; see Chapters 44, 78). 



The toxin of CI. oedematiens is the most potent of the gas-gangrene toxins ; 

 the average M.L.D. for a mouse is about 0-0002 ml. ; of welchii toxin the M.L.D. 

 is about 0-25 ml. ; and of CI. septicum toxin about 0-005 ml. 



Toxic filtrates of CI. septicum produce a marked liquefactive necrosis of muscle ; 

 lethal doses, when given intravenously, produce intense capillary engorgement and 

 interstitial haemorrhages in the heart, with hyaline degeneration of the muscle 

 fibres, and a toxic nephrosis in the kidney of experimental animals (Pasternack 

 and Bengtson 1936). Filtrates may also contain a heemolysin and a hyaluronidase. 

 The hsemolysin has usually been regarded as distinct from the lethal toxin ; but 

 Bernheimer (1944) has produced filtrates in which the lethal and the haemolytic 

 activities are substantially parallel. 



Toxic filtrates of CI. oedematiens contain a potent toxin that produces intense 

 gelatinous oedema in muscle. There are few gross changes in the organs following 

 a lethal intravenous dose of toxin, but degenerative changes, particularly in the 

 spleen and kidney, have been observed (Pasternack and Bengtson 1940). Traces 

 of lecithinase, a hyaluronidase and a heemolysin are sometimes present. 



CI. histolyticum usually produces a weakly toxic filtrate that contains an active 

 proteolytic enzyme. Toxigenic strains of CI. bifermentans have been described 

 under the name of CI. sordellii ; the filtrates are moderately toxic. All the toxins 



