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DISCUSSION 



Stocker: It has been suggested that strains of Neisseria, resistant to 

 sulphonamides, have an increased abihty to synthesize PAB. Is there 

 any suggestion of that kind of resistance in Pneumococcus in addition to 

 the more coinplex one? 



Hotchkiss: We don't see it in these strains, and I have never seen it. 

 The argument against it is that when we swamp the PAB which the cells 

 are endogenously making, by supplying PAB in the outer medium, we 

 still retain the same relative resistance level, the relation between 

 different mutants remains the same, even when we add so much that it 

 takes 150 times as much sulphonamide to block growth. 



Pontecorvo: Do I remember correctly that in a case of Neiirospora 

 sulphonamide resistance, there is an increase in endogenous production 

 of PAB? 



Davis: I don't know about simple resistance, but the sulphonamide- 

 dependent Neurospora mutant does not make more PAB. It is inhibited 

 by an imbalanced biosynthesis resulting from abnormal responsiveness 

 to its normal amount of PAB. 



Lederberg: In the control of resistance to penicillin is there a funda- 

 mental difference in the interaction of the genes ? 



Hotchkiss: The higher level of penicillin never gave rise to any low 

 level other than those particular low steps known to be reached during 

 its derivation, in a certain sequence. 



Lederberg: So that the interactions are presumably specific? Are you 

 distinguishing the levels purely by phenotype ? Because it may be that 

 there are several different mutations which simply give the same level of 

 resistance when you have only one of them, but which may interact to 

 give higher levels, which could be looked for by transformations among 

 the first ones. 



Hotchkiss: We tried transformations among them. We took highly 

 resistant donors, recovered all of the low-level transformants that they 

 produced as a mixed culture, made DNA from the mixed culture and 

 generally tested both mixed culture and DNA to see if either contained 

 anything from a higher level; whatever it may have contained was too 

 little to show. It may well be that there are hidden members of the 

 population that have acquired the factor b or c, but that show no penicillin 

 resistance. 



DRUG RES. — 7 



