Drug Resistance in Bacteria 21 



strains. Bad. lactis aerogenes, for example, will grow without 

 previous adaptation in presence of proflavine at concentra- 

 tions several times greater than those which completely 

 inhibit the growth of most strains of Esch. coli. 



The biochemical history of the strain also affects the 

 natural resistance level. A strain of Esch. coli transferred from 

 a broth medium to a minimal glucose-ammonium sulphate 

 medium acquired substantially increased resistance to pro- 

 flavine (in the minimal medium) as it became thoroughly 

 adapted to the medium itself. The maximum concentration 

 of proflavine tolerated rose about threefold (McConnell, 

 unpublished). Adaptation of Esch. coli to various nutrient 

 sources caused changes in the resistance level to various drugs 

 within a range of 50 to 150 per cent. 



These relatively minor diff'erences may be of structural 

 (genetic) origin, or may reflect changes in the enzymic 

 organization of the cell as the case may be. Cavalli-Sforza 

 and Lederberg (1956), by a selection technique with liquid 

 media, obtained strains which showed an increase from about 

 10 to about 35 mg./l. in the maximum concentration of 

 chloramphenicol which they would tolerate. We have, as 

 stated, observed variations of this order in the proflavine 

 resistance of mass cultures not subjected to selective tech- 

 niques, and the increase from 10 to 35 mg./l. in the chloram- 

 phenicol, even if it is due to the selection of mutants is very 

 small compared with the increase to many hundreds which is 

 readily achieved by culture in presence of the drug itself. A 

 strain of Esch. coli has been trained to resist 1,100 mg./l. of 

 chloramphenicol. 



With streptomycin, as with phage, much more drastic 

 increases in resistance have been reported (Lederberg and 

 Lederberg, 1952; Cavalli-Sforza and Lederberg, 1956). One 

 of the forms of streptomycin resistance is probably due to loss 

 of receptors for the drug, just as some phage resistance is due 

 to inability of the cell to take up the phage. This passive type 

 of resistance is, in our view, much more likely than any other 

 to arise spontaneously, since most controlled mutations seem 



