200 CHEMICAL NATURE OF ANTIBIOTIC SUBSTANCES 



and streptomycin, not only can they be readily differentiated from one 

 another by their bacteriostatic spectra, but the admixture of one with 

 the other can actually be measured quantitatively. B. mycoides can be 

 used to measure the presence of a small amount of streptomycin with 

 streptothricin, whereas bacteria resistant to streptomycin can be utilized 

 for detecting the presence of a small amount of streptothricin or other 

 antibiotic (858). 



Proactinomycin is produced by A^, gardneri grown in soft agar 

 media, from which it is extracted by organic solvents, such as ether, amyl 

 acetate, benzene, and carbon tetrachloride. It can be re-extracted in 

 water by adjusting the fH to 4.0 with HCl or H2SO4. The aqueous 

 extract is concentrated in vacuo and evaporated to dryness from the 

 frozen state. A white powder, very easily soluble in water, is obtained. 

 The yield of the material is 60 mg. from i liter of culture. The sub- 

 stance is fairly stable, though boiling for 10 minutes at /)H 2.0 or -pYL 

 7.0 results in a small loss of activity. Boiling at fH. lO.O destroys the 

 greater part of the antibacterial activity. Proactinomycin has basic prop- 

 erties and is precipitated from aqueous solution by such base precipitants 

 as picric acid, picrolonic acid, and flavianic acid. 



Proactinomycin is active in a dilution of i : 500,000 or more against 

 gram-positive cocci, B. ant hr acts y and N. meningitidis ; it is much less 

 active against gram-negative bacteria and is not very toxic to animal tis- 

 sues, but definitely more so than penicillin or streptomycin. When 

 given by mouth it can confer a considerable degree of protection against 

 intraperitoneal infection with hemolytic streptococci. It is excreted in 

 the urine and bile, and is absorbed from the alimentary canal. Repeated 

 injections cause fatty changes in the livers of mice (273). 



SUBSTANCES PRODUCED BY FUNGI 

 Penicillin 



Penicillin is produced by various strains of P. notatum and P. chry- 

 sogenunty as well as by a variety of other fungi. The penicillin-like 

 nature of an antibiotic substance is usually established by its chemical 

 and biological properties: extraction in organic solvents at ^H 2 and 

 re-extraction in water at ^H 7 ; inactivation by acid and alkali j partial 

 inactivation by heating at 100° C. and ^H 7 for 15 minutes j complete 



