In the solution there occurs a ptomaine, which has been isolated by Brieger, and which gives rise to almost all the phenomena of typhoid fever; this ptomaine is called typhotoxin.[130]
The same author, in collaboration with Fraenkel,[131] later on isolated a toxalbumin from the culture bouillon of the typhoid bacillus. Sanarelli[132] obtained an active toxin by macerating for several days at 60° C. a month-old culture of the typhoid bacillus made with a 2-per cent. glycerin-bouillon. Chantemesse has also published a process which yields a highly virulent toxin.[133]
Chantemesse and Widal[134] have shown that on injecting into an organism increasing quantities of the sterilized cultures of Eberth's Bacillus, it is possible to fully immunize an animal against the bacillus itself, and even also against the Bacillus coli communis. The operation, however, is tedious and painful. The serum of immunized animals possesses preventive and curative properties respecting the effects of typhoid bacilli.
A dose of the filtered culture, which is fatal to a guinea-pig, becomes innocuous when mixed with 0.5 Cc. of the serum of a vaccinated guinea-pig; 6 Cc. of the serum injected six hours after an injection of the virulent culture, hence when this is in full action, suffice to save the animal.[135] So far as the human being is concerned, the results obtained have not been sufficiently satisfactory.
The culture bouillon of the Bacillus coli communis, which is closely allied to Eberth's bacillus, also contains soluble toxic substances which have been named coli-bacillus toxin. This substance, which is produced only in small quantity by the microbe, is fatal only in very large doses.
Cholera Toxin.—Very little is known regarding the toxic products of the spirillium choleræ; nevertheless, the fact that typical cholera exhibits every symptom of the action of a toxic agent demonstrates quite clearly the elaboration of some toxic substance within the cultures of this microbe.
Villiers[136] found in it a liquid ptomaine; Klebs[137] found another and crystallizable ptomaine; while Pitai discovered in it a toxin unalterable by heat, and which he considered as a toxopeptone. According to Gamaleia[138] there is present a true toxin, alterable by heat, and the reactions of which entitle it to be considered as a nucleo-albumin; he has also found in it a toxic nuclein.
These toxic substances are found, according to Gamaleia, Pfeiffer, and Sanarelli,[139] confined during the life of the microbe within its cellular envelope, and does not diffuse through this. Metchnikoff and Roux are of the contrary opinion,[140] however, and they have prepared a toxin almost insensitive to a temperature of 100° C., and precipitable from its solutions by ammonium sulphate or strong alcohol; the toxin is a toxalbumin. This toxin is quite toxic; one-third of a cubic centimeter suffices to kill 100 Gm. of guinea-pig in 18 hours; with larger doses, death is almost immediate.
By immunizing guinea-pigs, rabbits, and horses with this cholera toxin, Metchnikoff and Roux obtained a serum which is distinctly antitoxic for rabbits. Nothing absolutely certain has been found as to its action on man.[141]