CHEMOTHERAPEUTIC AGENTS 155 



and the ability to adsorb glutamic acid is not impaired until 

 this process is taking place. From such results it may be 

 deduced that penicillin interferes not with nucleotide syn- 

 thesis but with their polymerization to nucleic acid. Park 

 and Johnson have noted that the gro\sth of Staph, aureus 

 in the presence of penicillin (i unit/ml.) leads to the accu- 

 mulation of intracellular compounds containing uridine- 

 5 -pyrophosphate and an unidentified amino carboxylic 

 sugar: a peptide of D-glutamic acid, D-valine and DL-lysine 

 is a component of one of these compounds, whilst another 

 contains L-alanine [i8]. Synthesis of such nucleotides only 

 occurs for as long as the cells are viable, and Park suggests 

 that they are natural intermediates whose utilization is 

 inhibited by penicillin. Maass and Johnson have shown that 

 part of the penicillin absorbed by a cell is irreversibly bound 

 within it, and they postulate that the antibiotic combines 

 with and thus inhibits the natural functioning of a cellular 

 constituent which is normally present in small amounts and 

 controls the processes of cell division [16]. 



Penicillin is lethal to most Gram-positive organisms and 

 is effective against only a few Gram-negative species, 

 whereas streptomycin, chloramphenicol and aureomycin are 

 active against a wide variety of organisms, and the two latter 

 are also valuable in the treatment of diseases due to viruses 

 and rickettsiae. Streptomycin had no effect on the accumu- 

 lation of glutamic acid by Staph, aureus, but in concentra- 

 tions markedly greater than those inhibiting growth, pre- 

 vented protein synthesis. Aureomycin and chloramphenicol 

 inhibited the absorption of glutamic acid and protein syn- 

 thesis, the latter being especially sensitive [6, 7]. Of the 

 many enzyme systems examined, only the diamine oxidase 

 activity of whole cells of Mycobacteria, Ps. aeruginosa and 

 Staph, aureus was inhibited by streptomycin, and there was 

 some evidence that inhibition of this oxidase resulted in the 

 cessation of growth [32]. Streptomycin contains basic 

 guanidine groups and a possible explanation was that it was 

 absorbed on to the enzyme in place of the natural basic 

 substrate. However, cell-free preparations of the oxidase 

 were but little affected by streptomycin, hence the observed 



