268 BACTERIOPHAGES 



The first recognition that chemical agents which inhibit the 

 action of phage can do so by preventing adsorption, ma}- be, 

 attributed to d'Herelle (1926). He explained the inhibition of 

 mass lysis by viscous colloids such as gelatin, agar, egg albumin, 

 and gums as a physical barrier between phage and host. Non- 

 viscous colloids such as colloidal silver and colloidal sulfur had 

 no effect. Though this concept may seem obvious in hindsight, 

 it was not so at the time and indeed the literature of that era 

 contains other more intricate explanations for the inhibitory ac- 

 tion of the colloids. 



The anatomy of the phage particle has been dissected suffi- 

 ciently to allow us to assign the function of attachment to a 

 particular structure. This apparently resides, at least in the T 

 series of coliphages, in the distal portion of the tail in the form of 

 protein strands which are wound like the fibers of a rope and 

 held together by disulfide bridges. Manipulations which alter 

 or destroy this portion of the tail will result in an inactivation 

 with respect to phage attachment. Kellenberger and Arber 

 (1955) achieved this with T2 and T4 phages by treatment with 

 hydrogen peroxide and ethanol. With this treatment the rope- 

 like distal sheath unravels and eventually dissolves leaving phage 

 particles with shortened tails. These bobtailed phages may 

 adsorb reversibly but they are unable to proceed to the irre- 

 versible step of attachment and hence can neither kill the host 

 nor establish infection. Kozloff and Henderson (1955) ob- 

 tained a similar distal decaudation of T2, but not of the other 

 T phages, by treating the phage with cyanide complexes of 

 metals of the zinc group, notably the anion Cd(CN)3. The rate 

 of inactivation of the phage correlates directly with the rate of 

 appearance of the bobtailed forms. These forms can neither 

 attach to nor kill the host cells. The modifications obtained by 

 these treatments are of particular interest since the phages un- 

 dergo similar changes when they normally adsorb to bacteria or 

 even to isolated bacterial cell walls. Brown and Kozloff (1957) 

 demonstrated that the cleavage of the tail upon adsorption is 

 required to expose an enzyme which dissolves the cell wall thus 

 paving the way for the injection of phage DNA. 



