CHEMICAL INTERFERENCE WITH PHAGE GROWTH 267 



3. Phage production may he inhibited without affecting 

 bacterial growth. This resuh is the essence of chemotherapy 

 and hence has received favored attention in the search for in- 

 hibitors. A number of screening programs, involving hundreds 

 of compounds, have been undertaken toward this aim. How- 

 ever, the producti\'e yield of promising agents which has come 

 from these heroic surveys has been disappointingly meagre. 

 Often there is only a narrow threshold between the concentra- 

 tions which inhibit bacteria and phage. Too often little attempt 

 is made to determine whether or not the agents exert a direct 

 inactivation of the phage, or to determine at what stage they 

 may act. Only those which have been more thoroughly studied 

 will be considered in later sections of this chapter, 



A variety of methods has been employed in studying the action 

 of chemicals as inhibitors of phage development. The nature 

 and the extent of the method is dictated by the purpose of the 

 analysis. Where the purpose involves a probing analysis of the 

 mechanism of action, all the available techniques must be called 

 upon. For the screening of a large number of compounds sim- 

 pler methods have been devised which allow for economy of 

 time and effort. Specialized and ingenious techniques are 

 described by Jones and Schatz (1946), Hall, Kavanagh, and 

 Asheshov (1951), Nicolle and Mimica (1947), and Hoshino 

 (1954a). These methods serve only as a convenient device for 

 selecting agents that may deserve further attention. The final 

 evaluation must depend on an analytical dissection of action at all 

 levels of phage multiplication. 



1. Prevention of Adsorption 



Phage growth can be prevented at the start by preventing 

 adsorption. This can be achieved by a variety of means: by 

 imposing a physical restriction such as viscosity ; by the destruc- 

 tion or alteration of that portion of the phage tail which is 

 required for adsorption ; by the destruction of the receptor sites 

 on the bacterial surface; by removing or competing with 

 cationic requirements; and by competing with organic cofactors. 



