Adaptation of Bacteria to Antibiotics 257 



not involving cell multiplication (Rotman and Spicgelman, 

 1953; Spicgelman, Sussman and Pinska, 1950; Campbell and 

 Spicgelman, 1956). The results of Spiegclman's research were 

 explained by assuming that new variants contained particles 

 necessary for enzyme formation, which were either lacking 

 or in insufficient numbers in negative, parental cells. 



For an explanation of the development of streptomycin 

 resistance in Esch. coll a similar mechanism is assumed. Some, 

 at present hypothetical, cytoplasmatic units whose nature 

 is now irrelevant for us, could be related to streptomycin 

 resistance. If the number of these units per cell is below 

 a certain level, the cell is susceptible to the drug action. If 

 the number of these units increases over a certain threshold, 

 cells become resistant due to the possibility of accumulation 

 of some metabolites, or alternatively of bypassing the bio- 

 chemical pathway sensitive to the drug or by another of the 

 possible mechanisms discussed by Davis (this symposium, 

 p. 165). 



There is some evidence, at present not yet fully documented, 

 supporting this assumption. Firstly, the stability of resistance 

 and the rate of the appearance of sensitive cells in media not 

 containing the drug is influenced by the temperature of 

 incubation. In some temperature ranges the process of rever- 

 sion is relatively rapid, in others it is distinctly retarded. 

 Secondly, the induction of resistance by cooling depends on 

 the physiological state of examined cells. It is inhibited in 

 initially starved cells, and its pattern is different in cells 

 harvested from nutrient broth (bacteria rich in metabolites) 

 and from synthetic medium (cells rich in enzymes). The 

 results of these experiments after their completion will be 

 the subject of future publications. Nevertheless, this hypo- 

 thesis, with no evidence against it, and some observations 

 supporting it, seems to be a convenient basis for further 

 research. 



It is assumed that genotypic change is, in our case, super- 

 imposed on a phenotypic one. Incubation in phosphate 

 buffer at low temperature w^ould then result in increase of the 



DRUG. RES. — 9 



