152 NITROGEN METABOLISM 



would appear that this antibiotic prevents the synthesis of 

 the systems responsible for the absorption of amino-acids 

 and does not affect the functioning of those systems once 

 they have been established. When washed suspensions of 

 cells grown for a short time with penicillin were incubated 

 with glucose and glutamic acid, little of the latter accumu- 

 lated in the cells, though extracellular peptides of glutamic 

 acid appeared in the system [7]. These results are analo- 

 gous to those of Hotchkiss, who used a different species 

 of staphylococcus and different experimental conditions. 

 Washed suspensions incubated with a mixture of various 

 amino-acids and glucose synthesized protein, but in the 

 presence of penicillin there was no increase in cellular com- 

 bined amino-acids though the number of free amino-groups 

 in the medium decreased. As in Gale's experiments, the 

 latter was correlated with the appearance of extracellular 

 peptides, and Hotchkiss suggested that penicillin inhibited 

 protein synthesis and that these peptides were either inter- 

 mediates in this process or were derived from them [13]. 

 Nevertheless, it is difficult to believe that penicillin inter- 

 feres directly with the synthesis of all proteins since it has 

 no effect on the formation of adaptive enzymes, a process 

 now regarded as being associated with the synthesis of new 

 protein. Streptomycin, aureomycin, chloramphenicol and 

 terramycin inhibit adaptive enzyme formation [11], an effect 

 which is possibly the outcome of interference with energy 

 metabolism. 



By examining a number of strains of Staph, aureus^ Gale 

 found that increased resistance to penicillin could be 

 correlated with a decline in ability to accumulate glutamic 

 acid. It will be recalled that Gram-negative, unlike Gram- 

 positive, organisms do not concentrate amino-acids in the 

 cells (p. 82), and the most highly resistant variants of 

 Staph, aureus obtained by successive subculture in increas- 

 ing concentrations of penicillin were in fact Gram negative. 

 Moreover, these organisms were no longer cocci but rod- 

 shaped and had lost the ability to utilize certain sugars and 

 grow anaerobically. Several workers have noted one or more 

 of these effects (i.e. changes in morphology. Gram-staining 



