CHEMICAL INTERFERENCE WITH PHAGE GROWTH 271 



adsorption but inhibits phage production only when added 

 before the phage (Kleczkowski and Kleczkowski, 1954). An- 

 other potent chelating agent, 8-hydroxyquinoline, is also known to 

 inhibit phage production (Wooley, Murphy, Bond, and Perrine, 

 1952). 



Hershey and Chase (1952) have shown that when T2 is 

 treated with formaldehyde, it is rendered incapable of injecting 

 its DNA into the cells to which it attaches. The inactivated 

 phage can still adsorb to and kill the bacteria but this adsorption 

 does not sensitize the phage DNA to deoxyribonuclease. Sev- 

 enty per cent of the adsorbed phage DNA can be detached from 

 the bacteria in a form which is still resistant to the action of de- 

 oxyribonuclease. It is apparent from this experiment that 

 formaldehyde inactivates an ingredient of T2 phage which is 

 required for the injection process. Brown and Kozloff (1957) 

 have shown that a phage enzyme is involved in this step. This 

 enzyme which is located in the tail of the phage and paves the 

 way for injection by dissolving the cell wall might well be the 

 site of inactivation by formaldehyde. 



3. Inhibition at the Intracellular Level 



Since the two major constituents of the phage particle are pro- 

 tein and DNA, we can largely restrict our discussion of direct 

 interference with phage synthesis to the processes concerned 

 with the synthesis of the two macromolecules. Because the 

 phage itself is devoid of any independent metabolic activity, 

 many reactions which are required for the synthesis of phage 

 protein and phage DNA must be operative in uninfected bac- 

 teria. The same conclusion follows from the vast number of 

 agents that suppress phage synthesis and bacterial growth 

 equally. This aspect of the problem is relevant only when the 

 attention of the investigator is focused on differential inhibition 

 and chemotherapeutic response. It becomes irrelevant when 

 the analysis is concerned primarily with the sequence and inter- 

 dependence of biosynthetic steps. 



Agents which prevent the synthesis of protein and nucleic 



