POISONOUS BACTERIAL PROTEINS 125 



animals.''- Animals immunized against endotoxins develop in their serum sub- 

 stances that arc bactericidal and agglutinative to the bacteria from which the 

 poisons are derived, but the serum will not neutralize the endotoxins. As a re- 

 sult, we are unable to perform experiments indicating whether endotoxins have 

 the same structure as the true toxins, i. e., a haptophore and a toxophore group, 

 but presumablj- their nature is different in some essential particular. The chemical 

 nature of the endotoxins is also unknown, for they are always obtained mixed with 

 the other constituents of the bacteria.*' 



Tuberculin, once supposed to be an albumose, is produced even when the bacilli 

 are grown on a protein-free medium, and in the active solution no albumose or 

 other protein is then found. Hence it seems probable that tuberculin is of the 

 nature of a polypeptid, which gives no biuret reaction but fs destroyed by pepsin 

 and trypsin, according to Loevenstein and Pick,*^ but not by erepsin (Pfeiffer).** 

 Whether tuoerculin should be considered an endotoxin liberated by the disintegra- 

 tion of the bacilli in the cultures is unknown; Pick looks upon it as a secretion of 

 the bacilli, and closely related to the true toxins. 



Since far more bacterial diseases are brought about by endotoxins than by true 

 toxins, the failure to secure antitoxins for these substances has been a great check 

 in the progress of serum therapj', and the problem of the endotoxins is one of the 

 most important in the entire field of immunity. 



Poisonous Bacterial Proteins 



If we filter a Iwuillon culture of diphtheria bacilli through porcelain, wash 

 thoroughly with salt solution the bacteria remaining, and collect them thus freed 

 from their secretion products, it will be found that extracts of the bacterial subtance 

 or the bodies of the killed bacteria themselves are quite free from the typical toxin. 

 This indicates that the toxin is eliminated from the bacteria as fast as it is formed, 

 and no considerable quantity is retained within the cell. The bacterial substance, 

 however, or proteins isolated from it, is found to produce severe local changes 

 when injected into the bodies of animals, necrosis and a strong inflammatory reac- 

 tion with pus-formation being the chief features. This local effect is not a specific 

 property of the diphtheria bacillus, for other bacterial proteins, including proteins 

 from non-pathogenic bacteria, will produce the same changes; indeed, many 

 proteins that are derived from vegetable and animal sources have equally marked 

 pyogenic properties. All foreign proteins when introduced into the circulation of 

 animals are more or less toxic, and the toxic effects of the bacterial proteins are, 

 for the most part, neither specific nor particularly striking. There are a few 

 pathogenic organisms, however, which seem to produce neither true toxins nor 

 endotoxins, notably the tubercle bacillus and the anthrax bacillus, and with these 

 there may be a relation between their protein constituents and their specific effects. 



Numerous protein substances have been extracted from bacterial cells, partic- 

 ularly nucleoproteins, but also proteins resembling albvmiins, nucleo-albumin, and 

 globulins. In all probability the chief proteins of the bacterial cell are nuclein 

 compounds, which is indicated both by their nuclear staining and by the anah'ses 



" Positive results are claimed by Besredka (Ann. Inst. Pasteur, 1906 (20), 

 304), and some others; see Kraus, Wien. klin. Woch., 1906 (19), 655; Zeit. Im- 

 munitiit., 1909 (3), 6-16. It is suggested by Wasisermann (KoUe and Wasser- 

 mann's Handbuch, 1912 (2), 246) that this difficulty in obtaining antiendotoxins 

 depends on the large size of the molecule, — the small diffusible toxin molecule is 

 so altered in its physical condition through union with the antibody that its 

 properties are much altered, whereas the large endotoxin molecule must be di- 

 gested by complement before its toxicitj- is destroyed. 



*^ The Aggressins of Bail, to which he ascribes the pathogenicity of bacteria, 

 are too little established to permit of a discussion from the chemical standpoint. 

 By many they are believed to be nothing more than endotoxins. (Literature 

 given by Miiller, Oppenheimer's Handb. d. Biochem., 1909 (II (1) ), 681; Dud- 

 geon, Lancet, 1912 (182), 1673). According to Ingravelle (Ann. d' ig. sperim., 



1910 (20), 483), tvphoid aggressins are found in the albumins. 

 5^ Biochem. Zeit., 1911 (31), 142. 



" Wien. khn. Woch., 1911 (24), 1115; see also Lockmann, Zeit. phvsiol. Chem., 



1911 (73), 389. 



