272 BACTERIOPHAGES 



acids may operate by interfering with nonspecific energy- 

 yielding reactions, by preventing synthesis or polymerization of 

 the essential building blocks, or by interfering with the synthesis 

 or function of specific cofactors. Numerous agents of many 

 types are known to inhibit both phage and bacteria and no 

 attempt will be made to list them here. The effects of literally 

 hundreds of compounds are reported in several heroic surveys 

 (Wooley, Murphy, Bond, and Perrine, 1952; Bourke, Robbins, 

 and Smith, 1952; Graham and Nelson, 1954). 



a. Interference with Energy Metabolism 



The over-all energy supply of the bacterial cell is furnished 

 through an integration of enzymes involved in the uptake of 

 oxygen and the transport of electrons, the oxidation and fer- 

 mentation of utilizable carbohydrates, the formation of energy- 

 rich phosphate bonds, and the regeneration of essential co- 

 enzymes. Upon infection with phage, the over-all energy 

 supply remains the same but it is now directed toward the 

 synthesis of phage rather than bacteria (Cohen and Anderson, 

 1946; Cohen, 1949). The action of enzyme poisons which are 

 known to be inhibitors of energy production further serves to 

 indicate that the energy supply which is essential for phage 

 synthesis is a product of the enzyme activities of the bacteria. 

 The synthesis of a variety of phages can be completely pre- 

 vented by azide, cyanide, fluoride, arsenite, iodoacetate, and 

 2,4-dinitrophenol. With few exceptions, the multiplication of 

 the uninfected bacteria is also inhibited. The exceptions are 

 reported in terms such as "little," "not appreciable," "essen- 

 tially inactive," or "materially unaffected." At any rate, 

 differential action is observed only over a limited and, in some 

 cases, very narrow range of concentrations. Some differential 

 impairment of phage synthesis was obtained with cyanide 

 (Dolby, 1955; Czekalowski, 1952), arsenite (Dolby, 1955; 

 Asheshov, Hall, and Flon, 1955), fluoride (d^Herelle, 1926) and 

 2,4-dinitrophenol (Fitzgerald and Babbitt, 1946; Czekalowski, 

 1952). 



