CHEMICAL INTERFERENCE WITH PHAGE GROWTH 277 



of the coenzymes. As inhibitors of phage production, special 

 consideration may be given to the antimetabolites of /^-amino- 

 benzoic acid, niacin, and pyridoxine. 



In the presence of sulfanilamide, /?-aminobenzoic acid is 

 required for the growth of E. coli B. The requirement can be 

 progressively decreased by successive additions of methionine, 

 xanthine, thymine, and valine, all of which are end products 

 whose syntheses require the participation of a coenzyme derived 

 from /^-aminobenzoic acid. The coenzyme, presumably a folic 

 acid derivative, mediates the transfer of single carbon units. 

 Rutten, Winkler, and DeHaan (1950) looked for a /?-amino- 

 benzoic acid requirement for phage production by infecting 

 bacteria which, in medium supplemented with the end product 

 metabolites, are permitted to grow in high concentrations of 

 sulfanilamide. Phage production was obtained. However, if 

 the bacteria were first grown in the sulfanilamide-metabolite 

 medium and were then infected, they no longer supported the 

 growth of T2, T4, and T6 coliphages, but could still produce Tl, 

 T3, and T7. The inhibition of T2 and its relatives could be 

 relieved by /^-aminobenzoic acid. This indicates that growth of 

 the T2-like phages requires a metabolite different from those 

 that suffice for growth of bacteria and other phages. This 

 metabolite should differ from others by one carbon atom. A 

 promising candidate is 5-(hydroxymethyl)cytosine. Cohen 

 (1953b) considered this possibility but his results were dis- 

 appointing since the inhibition of T4 by sulfanilamide could not 

 be reversed by 5-(hydroxymethyl)cytosine or its deoxyriboside, 

 or by 5-(hydroxymethyl)uraciI. 



Deoxpyridoxine can prevent the liberation of phage under 

 conditions which do not affect bacterial growth (Wooley and 

 Murphy, 1949; Asheshov, Hall, and Flon, 1955). Since its 

 inhibitory effects are reversed by various organic acids as well as 

 pyridoxine, its role as a specific antimetabolite cannot be 

 accurately assessed. Furthermore, suflScient analyses have not 

 been made to determine whether the inhibitory effects are di- 

 rected against internal metabolism or against some other stage 



