178 



Bernard D. Davis 



cells to inhibition of oxidation of a variety of substrates, 

 whereas disrupted cells of the two strains fail to show this 

 difference (Kushner, 1955). 



In closing, I should like to emphasize several consequences 

 of these recent developments for the study of antimicrobial 

 action and of drug resistance. First, compounds that reverse 

 an inhibition are not necessarily metabolites ; they can also be 

 analogues that interfere with penetration of the inhibitor. 

 This concept finally furnishes a plausible explanation, for 

 example, for the previously puzzling observation (Davis and 



Table II 



Uptake of i^C-d-sertne during growth 



Maas, 1949) that D-serine inhibition, though clearly located at 

 pantothenate synthesis, could also be reversed by a variety of 

 metabolically unrelated amino acids. Secondly, alterations in 

 permeability are not necessarily restricted to the cell mem- 

 brane, since subcellular particles are also present in bacteria, 

 and might be the site of a permeability barrier. Hence, when 

 studies of drug concentration in resistant cells fail to show a 

 marked decrease in permeation into the cell as a whole, the 

 possibility of a change in a permeability barrier has still not 

 been excluded. Finally, in a diploid bacterium, streptomycin 

 resistance has been shown to be genetically recessive to sensi- 

 tivity (Lederberg, 1951). This observation would be difficult 

 to understand if resistance were due to a qualitative or quanti- 



