338 THE BACTERIOPHAGE 



addition of its sulphone derivatives, amino-methane sulphonic acid, and that the 

 inhibiting action displayed by sulphanilamide was antagonized by y-aminobenzoic 

 acid (see Chapter 6). 



The Factors that Determine Phage Specificity. 



It has been well established, from the earliest days of bacteriophage study, 

 that any given strain of phage has a relatively limited range of activity. A coli- 

 phage, for instance, will not act on a staphylococcus, or on a diphtheria bacillus. 

 It was soon found, however, that phage specificity, while varying widely in range 

 with different strains of phage, might be much narrower than this. A coli-phage 

 would act on some strains of Bad. coli, but not on others, and so on. The obvious 

 assumption was that different strains of the same bacterial species differed in 

 " phage sensitivity," but no attempt was made by the earlier workers to determine 

 on what factors this sensitivity depended. A very significant advance in our 

 knowledge of this problem has been made by the studies of Burnet and his 

 colleagues. 



In a study of the activity of different strains of phage on the species and types included 

 within the Salmonella group of bacteria, it was found (Burnet 1927) that there was a 

 close relation between the sensitiveness of different bacterial species, or tjrpes, to a particular 

 phage, and the distribution of particular siu-face somatic antigens. Thus, a particular 

 phage was active against Salm. typhi, Salm. enteritidis and Salm. pullorvm, all of which 

 possess the somatic antigen IX, but was inactive against Salm. paratyjM A and Salm. 

 cholerce-suis, which do not possess this antigen. If, however, the normal smooth strains 

 of these species were replaced by their rough variants, in which the smooth somatic antigens 

 are lost, their place being taken by a common rough somatic antigen, then a phage that 

 attacked one rough variant would attack all the others. Some phages were found to attack 

 only the normal smooth forms, their range of activity then being determined by the dis- 

 tribution of the various smooth somatic antigens. Other phages attacked only rough 

 forms. A few phages were able to attack both rough and smooth forms (Burnet 

 1929a). 



Further study revealed similar correspondence between antigenic structure and sensi- 

 tivity to various phages. Schmidt (1931) noted that different species of salmoneUa 

 bacilli could be differentiated by their sensitiveness to different selected phages. In some 

 cases the correspondence is exact, in others less so. Lately it has proved possible to 

 extend the range of phages specific for different antigenic varieties of certain bacterial 

 species by adapting phages to antigenic types for which at first they show httle affinity. 

 For example, following the discovery that the action of certain phages on Salm. typhi 

 depended on the presence of the Vi antigen of Fehx and Pitt (1934) (see Sertic and Boul- 

 gakov 1936a, Scholtens 1936, 1937, Craigie and Brandon 1936a), Craigie and Yen (1938) 

 were able to develop phages with selective action against 1 1 different varieties of Salm. typhi. 

 In a similar manner Fehx and Callow (1943) were able to adapt naturally occurring phages 

 active against Vi forms of Salm. paratyphi B, and so extend the range of phages selective 

 for different varieties of the bacilh. It will be obvious that once the correspondence 

 between a bacterial and phage type is established, bacterial strams may be identified 

 and assigned to a given phage type by tests with known strains of phage. 



In many cases, a group of bacteria, homogeneous by serological tests, proves on phage 

 testing to consist of a number of stable sub-types. The recognition of these sub-types, 

 as Craigie and Yen first demonstrated, adds greatly to the precision of bacteriological 

 surveys for epidemiological purposes. (See also Helmer, Kerr, Dolman and Ranta 1940, 

 Lazarus 1940, 1941, Dolman, Kerr and Helmer 1941, Desranleau 1942, Hutchinson 1943, 

 Felix 1943.) 



There are a number of bacterial species in which the relationship of antigenic structure 



