THE INITIATION OF BACTERIOPHAGE INFECTION 217 



It was pointed out recently (Hersliey, 1957a) that it may not be valid to 

 draw any conclusions about the collision efficiency of the phage attachment 

 reaction on the basis of diffusion theory alone. The Schlesinger calculation 

 can be used to evaluate the rate of collisions between phage particles and cells 

 only in cases where attachment occurs with perfect efficiency. If every colli- 

 sion does not lead to attachment, the phage concentration at the cell surface 

 becomes finite instead of zero, and the rate of collisions can no longer be 

 evaluated by the method of Schlesinger. It has been concluded that the col- 

 lision efficiency of attachment of Tl, T2, and T4 is essentially perfect because 

 of the close agreement between the measured rate of attachment and the 

 theoretical maximum rate calculated from the Schlesinger equation. How- 

 ever, a possible discrepancy between the measured and theoretical rates of 

 as much as 50 % has not been excluded. A discrepancy of this magnitude 

 does not mean that the collision efficiency also is 50 %. The efficiency may 

 be considerably lower, since a phage particle that diffuses to the cell surface, 

 but does not attach on the first collision, is likely to collide several times 

 more before diffusing away. 



VI. Genetic Control of Attachment Specificity 



A. Resistant Cell Mutants 



In a large population of bacterial cells, aU descended from a single phage- 

 sensitive parent, there can usually be found some cells that are phage- 

 resistant (i.e., are not killed by exposure to the phage). Resistant cell strains 

 have been shown to originate from random mutational events that occur 

 during the multiplication of the sensitive strain (Luria and Delbriick, 1943). 

 In general, it has been possible to obtain resistant cell mutants with all the 

 kno^vn phage-host systems. When the parental strain is sensitive to many 

 different phages, as with E. coli B, sensitive to the seven T-phages, a muta- 

 tion may impart resistance only to one phage (e.g. B/6, resistant only to T6) 

 or simultaneously to several (e.g., B/3, 4, 7, resistant to T3, T4, and T7). 

 Resistance to several different phages can also develop by successive indepen- 

 dent mutations. 



A phage generally cannot attach to the bacterial mutant that is resistant 

 to it. This kind of ceU mutation, therefore, must affect the cell surface. The 

 fact that resistance may be selective for only one of the phage strains active 

 on a cell indicates that different strains may attach to different cell sites and 

 that the surface modifications responsible for resistance are localized at or near 

 the attachment sites for a particular phage. In cases where resistance can 

 develop simultaneously to several different phage strains, the phages involved 

 in the pattern of resistance probably use overlapping attachment sites 



