Genetic Aspects of Drug Resistance 53 



and dependence (Demerec, 1950; Neweombe and Nyholm, 

 1950), and that a linkage relationship exists between strep- 

 tomycin resistance and a methionine marker (Lederberg et al., 

 1952). Other studies made with the K 12 strain have shown 

 that any one of several gene loci — four or five at least — may 

 be responsible for the inheritance of a low degree of resistance 

 to chloramphenicol (Cavalli and Maccacaro, 1950, 1952). 

 It has also been established that one gene locus is responsible 

 for a low degree of resistance to azide, and that it is closely 

 linked with the locus controlling resistance to bacteriophage 

 Tl (Lederberg, 1947). In this case, further experiments 

 using the two linked markers have demonstrated segregation 

 conforming to Mendelian expectation (Cavalli, 1952). Work 

 done by several investigators has shown that the genes 

 governing resistance to certain drugs (streptomycin and azide), 

 as well as those involved in resistance to some phages, are 

 distributed more or less indiscriminately among other gene 

 loci; and there is no reason, at least from their positions on 

 the chromosome, to assume that they are in any way excep- 

 tional as compared with other bacterial genes. 



Transformation and transduction analyses 



Two unique mechanisms have been discovered whereby 

 genetic properties — presumably conveyed in genes or chro- 

 mosomal fragments — may be transferred from one bacterial 

 strain to another. In transformation, the transfer is accom- 

 plished by deoxyribonucleic acid (DNA) extracted from 

 donor cells and brought into contact with the recipient bac- 

 teria, whereas in transduction phage particles act as vectors. 

 Genetic markers that have been used successfully in transfor- 

 mation experiments include resistance to penicillin, strep- 

 tomycin, and sulpha drugs (Hotchkiss, 1951; Alexander and 

 Leidy, 1953); and transduction has been used to study strep- 

 tomycin resistance (Zinder and Lederberg, 1952; Baron, 

 Formal and Spilman, 1953; Iseki and Sakai, 1954). Thus, in 

 this respect also, drug resistance corresponds to other pro- 

 perties that are controlled by genes. 



