ANTIBACTERIAL ACTION 241 



pletely neutralized or antagonized by various chemical agents. These 

 include glucose and certain other sugars, an anaerobic environment, 

 certain sulfhydryl compounds, and ketone reagents. In some cases, as 

 in the action of sugars or the anaerobic environment, the effect on strep- 

 tomycin may be traced to the acidity produced under these particular 

 conditions. However, in the effect of cysteine, of cevitamic acid, and of 

 ketone reagents the inhibition of streptomycin activity may be asso- 

 ciated with the blocking of the active grouping in the molecule of the 

 streptomycin. Streptomycin represents too large a molecule to explain 

 the inactivation of its antibacterial properties by the blocking of a single 

 group in its molecule. Until the chemistry of streptomycin is more 

 clearly elucidated, it is difficult to present a suitable theory that would 

 explain the various effects of streptomycin inactivation (327). 



The ability of various bacteria to give rise to strains which are more 

 resistant to the action of streptothricin and streptomycin has been defi- 

 nitely established. Certain strains have been obtained that are a hun- 

 dred or more times as resistant to streptomycin as the original culture. 

 Such strains are only slightly more resistant to streptothricin, and show 

 no difference from the mother culture in their sensitivity to penicillin, 

 clavacin, or antibiotics of spore-forming bacteria. Variations in sensi- 

 tivity to streptomycin by natural strains of the same organism have also 

 been obtained (965). This phenomenon has an important bearing upon 

 the chemotherapeutic utilization of the material. 



Streptothricin-resistant strains of L. easel show differences in panto- 

 thenic acid and biotin sensitivity from the susceptible parent strains 

 (716). 



Actinomycm 



Actinomycin is a bacteriostatic agent, active primarily against gram- 

 positive bacteria. It is extremely toxic to animals, a factor which limits 

 its practical utilization. One milligram of actinomycin given to mice, 

 rats, or rabbits intravenously, intraperitoneally, subcutaneously, or 

 orally proved (796) to be lethal for i kilogram weight of the animals. 

 Doses as small as 50 Mg per kilogram injected intraperitoneally daily 

 for 6 days caused death accompanied by severe gross pathological 

 changes, notably a marked shrinkage of the spleen. Actinomycin is 



