TOXINS OF FUNGI 127 



to time, there are found cavities in the lungs and a massive growth of 

 mycelium in the air sacs. 



Toxins of Fungi. It is not clearly understood how the pathogenic 

 fungi injure the tissues. Although fibrosis and giant cell reactions 

 about some lesions bear a resemblance to a foreign body reaction, 

 the extensive necrosis and suppuration which occur in the center of 

 most lesions cannot be readily explained in this way. Moreover, the 

 experimental lesions produced with freshly isolated and highly viru- 

 lent strains of some species, as Aspergillus fumigatus and Candida 

 albicans, are so acute as to suggest that these diseases may be caused 

 by the same mechanisms as those found in bacterial infections. A 

 pigeon inoculated intravenously with a suspension of spores of A. 

 fumigatus may die within 24 hours, showing at autopsy multiple 

 punctate hemorrhages and areas of degeneration or necrosis in par- 

 enchymatous tissues, in short, just such a picture as may be pro- 

 duced by a highly virulent Streptococcus. Such findings naturally 

 suggest that a potent toxin is formed. 



Considerable investigation has been carried on with regard to 

 the toxins of other pathogenic fungi, but it is largely contradictory 

 and inconclusive. No exotoxins have been definitely established. 

 The occurrence of endotoxins is of considerable theoretical interest. 

 Our conception of endotoxins is based largely upon the demonstra- 

 tion of endoenzymes by Buchner's classical experiment. It is not 

 possible to express the cell sap of bacteria by pressure, as Buchner 

 did with yeasts, because of their minute size. All other attempts to 

 remove toxins from within the cells of bacteria by chemical extrac- 

 tion, autolysis, grinding (after drying or freezing) may be criticized 

 as introducing factors that might readily alter the toxins. How- 

 ever, the cell sap of molds may be expressed readily in a Buchner 

 press. It is remarkable that very few attempts to obtain a toxin 

 from pathogenic fungi by this method are recorded in the literature. 



Gortner and Blakeslee,^^ during the course of some experiments 

 dealing with antibody production, accidentally discovered that the 

 cell sap of Rhizopus nigricans is highly toxic to rabbits. The toxic 

 substance was obtained both by expressing the juice of the mold 

 and by extraction of dried mycelium with hot water. It gave the 

 reactions of proteins, was non-dialyzable, and was precipitated by 

 alcohol. Intravenous injections in rabbits produced almost imme- 

 diate death, with both symptoms and autopsy findings "practically 

 indistinguishable from anaphylactic intoxication." Subcutaneous in- 

 jections gave rise to abscesses which broke down to form ulcers. The 

 material was quite harmless by mouth. It is quite possible that these 



