126 BACTERIOPHAGES 



test of Luria and Delbruck (1943), the replica plating technique 

 of Lederberg and Lederberg (1952), and the redistribution test of 

 Newcombe (1949). Methods for the determination of mutation 

 rates have been discussed by Newcombe (1948), Lea and 

 Coulson (1949), and Armitage (1953). Measured mutation 

 rates to phage resistance are of the order of 10 ~^ to 10~^° muta- 

 tions per bacterial division. 



Mutation to phage resistance may involve any of a number of 

 distinct physiological mechanisms. Resistance to infection cor- 

 related with the failure of phage adsorption has been noted 

 above. Lack of adsorption may be due to the absence of the re- 

 ceptor substance to which the phage particle normally becomes 

 attached. When this receptor substance happens to be a major 

 antigen of the bacterial cell, its loss by mutation may be readily 

 detected by immunological techniques. If the receptor substance 

 is nonantigenic or is a minor antigen, it may be more difficult to 

 discover the reason for failure of adsorption. Failure of adsorp- 

 tion may also be due to the covering of the receptor substance by 

 some other bacterial layer, as in the mutation from rough to 

 smooth in the salmonellas. In this case the acquisition of the O 

 antigen results in loss of susceptibility to the "rough specific" 

 salmonella phages (Burnet, 1930). Mucoid variants of phage- 

 susceptible bacteria are usually phage-resistant because the 

 masses of slime material interfere with phage adsorption (Gratia, 

 1922). Doubtless other mechanisms may play a role in the 

 acquisition of phage-resistance by mutation, but these have not 

 been studied. 



Phage-resistant mutants of bacteria very often retain a normal 

 susceptibility to some phages while becoming resistant to others. 

 Such mutant strains are of considerable value in phage research 

 since they can be used as specific indicators to demonstrate the 

 presence of a particular strain of phage in a mixture. 



The nomenclature used for phage-resistant mutants was origi- 

 nated by Burnet and McKie (1933) and modified by Demerec 

 and Fano (1945). Strain B of E. coli is susceptible to phage-Tl 

 through T7. A phage-resistant mutant isolated by means of 



