280 BACTERIOPHAGES 



lysis of bacteria infected with a coliphage at a very low multi- 

 plicity of infection. The concentrations used were insufficient 

 to prevent the growth of uninfected bacteria. These observa- 

 tions revived interest in the acridines and a flood of reports 

 followed which confirmed the differential action of a variety of 

 acridines against a variety of phages. Table XVI summarizes 

 this work, which shows that not all phages are inhibited selec- 

 tively relative to their hosts. Mutant phages resistant to acri- 

 flavine have been isolated by selection (Foster, 1948; Mutsaars, 

 1951b; Hoshino, 1954b). Diff"erential inhibition cannot be 

 demonstrated with these mutants since they are now more 

 resistant than the bacterial host. 



The stage at which proflavine (2,8-diaminoacridine) prevents 

 the development of phage has been studied extensively. The 

 analysis by Foster (1948) separates phages into those (T2, T4, 

 T5, and T6) whose development is prevented by concentrations 

 which are 0.1 to 0.5 the concentration required to inhibit bac- 

 teria, and those (Tl, T3, and T7) which are inhibited only at 

 bacteriostatic concentrations. The activity of free phage and 

 its adsorption to bacteria are not affected by proflavine. Lysis 

 occurs after the normal latent period but no infectious particles 

 are found in the lysates. The same result is obtained when the 

 acridine is added at any time during the first half of the latent 

 period. When added later, the bursts yield only those phage 

 particles which had already matured before the addition of 

 proflavine. 



DeMars, Luria, Fisher, and Levin thai (1953) examined lysates 

 obtained in the presence of proflavine and found the same 

 "doughnuts" (empty phage heads) that had been seen in prema- 

 ture lysates not containing proflavine (Levinthal and Fisher, 

 1952). The phage heads contain sulfur and phage-specific 

 complement-fixing antigens but no DNA. The antigen which 

 combines with neutralizing antibody is also present in proflavine 

 lysates but can be separated from the phage heads. DNA con- 

 taining hydroxymethylcytosine is also found (DeMars, 1955), as 



