278 BACTERIOPHAGES 



of the infection sequence. The same reservation must be made 

 in evaluating the significance of the differential action of niacin 

 analogues such as 6-amino nicotinic acid (Woolcy, Murphy, 

 Bond, and Perrine, 1952) and isonicotinic acid (Bourke, Robbins, 

 and Smith, 1952). In the latter case an interesting observation 

 was made but not pursued. Lysates of T2 obtained in the 

 presence of isonicotinic acid killed bacteria on subsequent infec- 

 tion without the production of new phage progeny. 



/. Prevention of Ma Air ation 



Only one class of substances, the acridine dyes, are known to 

 prevent phage growth while permitting synthesis of phage pro- 

 tein and nucleic acid, but they are of special interest for that 

 reason. When bacteria are infected with T2 in the presence of 

 proflavine, synthesis of protein and DNA occurs and the bacteria 

 lyse as usual, but do not liberate infective particles (DeMars, 

 1955). Phage-specific elements are found, however, and one 

 can only suppose that some final step in the maturation of the 

 particles is blocked (Foster, 1948). 



This example is also exceptional because the effect depends on 

 the genotype of the phage. The growth of many phages is not 

 blocked by low concentrations of the inhibitor, and sensitive 

 phages can mutate to resistant forms (Foster, 1948). In the so- 

 called defective strains of lysogenic bacteria it is also possible to 

 show that phage mutations can aff"ect late steps in maturation 

 (Chapter XIX). Because of their potential value in the study 

 of phage morphogenesis, the effects of the acridines will be 

 discussed in some detail. 



The acridines gained prominence in the early days of chemo- 

 therapy as drugs which exhibited a remarkable degree of selec- 

 tive inhibition in protozoal diseases. Wolff" and Janzen (1922) 

 reported that trypaflavine (acriflavine) and rivanol can inhibit 

 "bacteriophagy" with four different phages at concentrations 

 too low to affect bacterial growth or destroy free phage particles. 

 This observation lay dormant for 24 years until Fitzgerald and 

 Babbitt (1946) found that 8 out of 11 acridines inhibit the mass 



