184 CHEMICAL NATURE OF ANTIBIOTIC SUBSTANCES 



205, 207) from certain soil bacteria. These enzymes are highly specific, 

 some being able to act only upon one type of pneumococci. As a result 

 of their action, the pneumococcus cell is rendered susceptible to destruc- 

 tion by phagocytosis. This enzyme was produced by the soil bacteria 

 under selective conditions of culture, that is, when the capsular polysac- 

 charide of the pneumococcus was present in the medium j the only other 

 substance that could be used for its production was aldobionic acid, 

 which was derived from the above polysaccharide. Yields of the en- 

 zyme were increased by increasing the concentrations of the specific 

 substrate in the medium from 0.0 1 to o.i per cent. Above o.i per cent, 

 the yields decreased, 0.3 to 0.4 per cent inhibiting the growth of the bac- 

 terium. The addition of 0.1 per cent yeast extract favored the produc- 

 tion of the enzyme j proper aeration was essential, the bacterium mak- 

 ing the best growth in shallow layers of medium. The enzyme was 

 concentrated by distillation in vacuo and by ultrafiltration. Toxic sub- 

 stances accompanying the active preparation could be largely removed 

 by the use of an aluminum gel. The enzyme is associated with a protein 

 which passes through a collodion membrane with an average pore size 

 of 10.6 (J, but is held back by pores having a diameter of 8.2 |j. After 

 filtration, the enzyme can be recovered in solution by immersing the 

 membrane in distilled water or in physiological salt solution. 



Dubos (199) believed that it is possible to develop "adaptive" bac- 

 terial enzymes against many organic substances. These enzymes exhibit 

 a great degree of specificity, as in the case of the enzyme that hydrolyzes 

 the capsular polysaccharide of the pneumococcus. The cell of this or- 

 ganism contains an enzyme that changes the cell from the gram-positive 

 to the gram-negative state, but is ineflrective against streptococci or 

 staphylococci. 



Active preparations of the enzyme protected mice against infection 

 with as many as i ,000,000 lethal doses of the specific pneumococcus. The 

 enzyme retained its activity for 24 to 48 hours after its injection into 

 normal micej it also exerted a favorable influence on the outcome of an 

 infection already established at the time of treatment. A definite rela- 

 tionship was found to exist between the activity of the enzyme in vitro 

 and its protective power in the animal body. 



