418 R. M. S. SMELLIE 



titative point of view, it is interesting to observe that the amount of these 

 derivatives of uracil present in the extracts of penicillin-treated cells must 

 represent a considerable proportion of the uracil which would be required 

 for the synthesis of PNA, and that on this basis one might expect to find 

 considerable inhibition of PNA synthesis. 



Gros and Macheboeuf^^'* have recently followed up their previous ob- 

 servations on the inhibition of the catabolism of certain nucleotides by 

 the treatment of S. aureus with penicillin, by an investigation of the ability 

 of nongrowing preparations of the organism to catabolize PNA, and various 

 derivatives of PNA, in the presence and absence of penicillin. They found 

 that there was appreciable inhibition of the oxidation of PNA, guanylic 

 acid, guanosine, and uridylic acid by S. aureus in the presence of high con- 

 centrations of penicillin. In the same conditions, however, the metabolism 

 of the other nucleotides, nucleosides, or of ribose and ribose-5-phosphate 

 was unaffected. It was therefore concluded that penicillin affects the nu- 

 cleosidase activity of the organism although very considerable differences 

 were found with different strains of the organism. 



These authors'^* have also studied the effect of small doses of the anti- 

 biotic on growing cultures of S. aureus. In this work it was found that cells 

 which had been treated with penicillin during the growth period and were 

 then separated from the medium and washed, showed greatly reduced 

 ability to oxidize guanosine or guanylic acid as compared with the normal. 



Gale and Folkes^^*'^" have also investigated the mode of action of peni- 

 cillin on the synthesis of nucleic acids by *S. aureus. They found that this 

 organism could synthesize' nucleic acids when the medium contained an 

 amino acid mixture. If this amino acid mixture were supplemented by a 

 mixture of purines and pyrimidines, the synthesis of nucleic acids was 

 greatly stimulated. High concentrations of penicillin (50 to 10,000 units 

 per ml.) caused some inhibition of the additional nucleic acid synthesis, 

 stimulated by the purine-pyrimidine mixture, without any effect on the 

 basic synthesis of nucleic acids. 



b. Aureomycin, Chloramphenicol, Neomycin, and Terramycin 



These four antibiotics fall into one class; at very high concentrations 

 they inhibit nucleic acid synthesis in S. aureus, but, at concentrations cor- 

 responding to those producing complete inhibition of growth, synthesis 

 of nucleic acids is actually stimulated. •^^"'^'^ 



1'^ F. Gros and M. Macheboeuf, 2nd Intern. Congr. Biochem., Paris p. 101 (1952). 

 '35 E. F. Gale and J. P. Folkes, Biochem. J. 53, 493 (1953). 

 "« E. F. Gale, 2nd Intern. Congr. Biochem., Paris p. 5 (1952). 

 '" E. F. Gale, Advances in Protein Chem. 8, 285 (1953). 



