CHEMICAL INTERFERENCE WITH PHAGE GROWTH 273 



Under special conditions where uninfected bacteria are un- 

 able to grow but can still produce phage when infected, phage 

 production is completely halted by respiratory poisons (Spizizen, 

 1943b; Price, 1947b). In the system described by Price, the 

 inhibition of phage synthesis in penicillin-inhibited staphylococci 

 by azide, fluoride, and iodoacetate is accompanied by a decrease 

 in ATP synthesis. 



Another action of the metabolic poisons is their ability to 

 promote lysis of infected cells (Cohen, 1949; Heagy, 1950; 

 Doermann, 1952; Anderson and Doermann, 1952a). When 

 bacteria are infected with the T2 or its relatives in the presence 

 of cyanide, iodoacetate, or 2,4-dinitrophenol, the adsorption of 

 only a few particles per cell immediately initiates lysis from 

 without with the loss of the adsorbed phage. This does not 

 occur with other phages. In all cases, lysis fails when the in- 

 hibitors are added during the early part of the latent period, 

 but the infecting phage is lost and subsequent production 

 does not occur. When added during the second half of the 

 latent period, premature lysis is induced with the liberation of 

 those active phages which have already been formed. 



b. Prevention of Protein Synthesis 



As indicated in Chapter XIV, bacteria which are unable to 

 synthesize amino acids as a result of either a physiological or 

 genetic impairment will not support the growth of phage unless 

 the medium is supplemented with the required amino acid. 

 Chemical interference with amino acid metabolism, and hence 

 protein synthesis, would be expected to result in a cessation of 

 phage formation. The inhibitors which have been examined 

 are structural analogues of natural amino acids. Analogues of 

 glycine, tryptophan, methionine, glutamic acid, and phenylala- 

 nine have been found to inhibit phage production as well as 

 bacterial multiplication. 



The first test of an amino acid analogue as an inhibitor of 

 phage synthesis was made by Spizizen (1943a). He found that 

 aminomethane sulfonic acid, a structural analogue of glycine, 



