266 BACTERIOPHAGES 



chemotherapy may be found in the reviews by Cohen (1949, 

 1953a) and by Matthews and Smith (1955). 



In this chapter we will deal only with those substances which 

 prevent the establishment of phage infection or prevent the 

 production of active phage progeny. Agents which have a 

 direct phagicidal action were considered in Chapter V and will 

 not be dealt with here unless the treatment which inactivates the 

 free particle has a consequential bearing on some stage of the 

 infectious process. The specific inactivation of phage by recep- 

 tor substances, which results in loss of adsorbing or penetrating 

 potentials, was described in Chapter X. 



To assess the action of a drug on phage production, its action 

 on the growth of uninfected bacteria should also be determined. 

 The results to be expected may be classified as follows. 



7. Both bacteria and phage may be inhibited. The majority 

 of the known inhibitors fall into this category. The nonselective 

 action is an obvious expression of the similar requirements for the 

 synthesis of phage and for the synthesis of bacterial protoplasm. 

 The substrates and enzymic processes which are required to sup- 

 ply energy and to permit synthesis of protein and nucleic acid are 

 equally indispensable for phage and bacteria. 



2. Bacterial growth may be inhibited without affecting phage 

 production. As indicated in Chapter XIV, viable bacteria are 

 not always essential for phage growth. Agents such as peni- 

 cillin (Price, 1947a), sulfur mustard (Herriott and Price, 1948), 

 and pentamidine (Boyd and Bradley, 1951; Amos and Voll- 

 mayer, 1957) allow phage production at concentrations which 

 completely inhibit the growth of the bacteria. In these cases we 

 must look for a metabolic process which is essential for the sur- 

 vival and growth of the bacteria but which plays no role in the 

 formation of phage. In the case of penicillin, the nature of such 

 a process has been revealed by the reports of Park and Strominger 

 (1957) and J. Lederberg (1957). Penicillin apparendy kills 

 bacteria by j^reventing the synthesis of cell wall material. Since 

 phage growth can occur in bacterial protoplasts, the maintenance 

 of the cell wall is not required for the synthesis of phage. 



