Chloromycetin Resistance in £. coli, a Case 

 of Quantitative Inheritance in Bacteria 



Drug resistance in bacteria has been investigated 

 genetically in several cases, since Demerec began 

 with penicillin resistance in Staphylococcus aureus 1 . 

 The proposal to distinguish two classes of drug 

 resistance — those in which the top level of resistance 

 can be obtained in a single step, and those in which 

 it can be acquired only gradually — has clearly a 

 practical importance ; its theoretical meaning has 

 not been entirely % elucidated, since genetical analysis 

 has several limitations in bacteria. In fact, while 

 mutational patterns are open to investigation in most 

 cases, crossings can only be regularly undertaken, 

 as in Lederberg and Tatum's original discovery 2 , 

 in a few strains of E. coll. In one of these, E. coli 

 K-12, some work on the genetics of drug resistance 

 has been carried out, the most extensive investigation 

 relating to streptomycin. Full resistance in E. coli 

 is developed in a single step 3 - 4 . 



Besides resistance, dependence is known, whereby 

 some resistant mutants fail to grow in absence of 

 streptomycin. Full streptomycin-resistance and 

 dependence 4 - 8 seem to be due to a single locus (or 

 closely linked loci). Further, Lederberg introduced 

 resistance to azide 6 as a genetic marker ; here a 

 single step brings about a moderate degree of resist- 

 ance, and the determining factor has been mapped, 

 not only in this laboratory but also independently 

 in two other laboratories, and found to be about 

 midway between V x and TL on the 'chromosome 

 map' of E. coli K-12. Nitrogen mustard resistance 

 was found to be gradual or abrupt in increase in 

 different experiments, only a moderate degree of 

 resistance being acquired, which made a detailed 

 analysis difficult. In E. coli K-12 nitrogen mustard 

 resistance is not accompanied by higher resistance to 

 radiations, as in the case of E. coli B. 



Completely 'gradual' increase of resistance has 

 been found in the case of Chloromycetin in E. coli 

 K-12. Selecting for Chloromycetin resistance by 

 serial transfers in liquid cultures containing increasing 

 concentrations of the drug (on a geometric scale), a 

 rapid and relatively smooth increase of resistance is 

 observed. Starting from a tolerated level of 5-10 

 [jgm./ml., as is usual with strains derived from the 

 original E. coli K-12, levels of resistance as high as 

 1,280 ijgm./ml. (which is not far from the solubility 

 limit of Chloromycetin) can be obtained. The increase 



[Reprinted by permission of MacMillan & Co. Ltd. from Nature 166:991, December 9, 

 1950] 



91 



