198 NATURE OF ANTIBIOTIC ACTION 



action of the substance, and some bacteria and fungi even may produce 

 an enzyme, such as penicillinase, that brings about the destruction of the 

 antibiotic substance. 



The antibacterial action of gramicidin was found (391, 401) to be 

 inhibited by a cationic detergent, phemerol, whereas penicillin was not 

 affected by either gramicidin or two cationic detergents, phemerol and 

 zephiran. When gramicidin and penicillin were used together, their 

 effect was only slightly additive (388) j however, penicillin and strepto- 

 thricin exerted a marked additive effect upon bacteria sensitive to both 

 of these substances (287). 



The inhibition of the antibacterial action of sulfanilamide by 

 /(-amino-benzoic acid has been explained by the fact that the latter is a 

 growth factor in bacterial nutrition (538, 813, 1003). Competition for 

 this growth factor between the bacterial cell and the bacteriostatic agent 

 is responsible for the inhibition of the agent. In a similar manner pan- 

 toyltaurine, which is related to pantothenic acid as sulfanilamide is to 

 ^-amino-benzoic acid, will inhibit the growth of hemolytic streptococci, 

 pneumococci, and C. difhtheriae, by preventing the utilization of panto- 

 thenic acid by these bacteria, for which it is an essential metabolite 

 (558). Fildes (254) emphasized that "chemotherapeutic research 

 might reasonably be directed to modification of the structure of known 

 essential metabolites to form products which can block the enzyme 

 without exhibiting the specific action of the metabolite." The antibac- 

 terial activity of iodinin is neutralized by quinones 5 this is probably due 

 to the destruction of the iodinin, since the N-oxide is reduced by the or- 

 ganism {SSS-) SS^)- Different anti-inhibitors are known for other anti- 

 biotic substances, as shown later. 



The concentration of the active substance and the composition of the 

 medium are highly important in modifying the activity of the sub- 

 stance. Some antibiotic substances, like penicillic acid, lose considerable 

 bacteriostatic activity when incubated with sterile broth or with sterile 

 peptone water at /)H 7 and 37° C. for i to 3 days (662) j a similar ef- 

 fect was observed with certain simple amines and amino acids. The con- 

 centration of the substances reacting with penicillic acid is diminished 

 on autoclaving the peptone broth in the presence of 2 per cent glucose. 

 The neutralizing or anti-inhibiting agent interacts with the antibiotic 



