Anfibiotic Research 175 



unchanged antibiotic. Finally, in contrast to penicillin- 

 sensitive bacteria, and like highly resistant organisms, cell- 

 free extracts of mammalian cells bind the antibiotic to 

 only a limited degree. 



The foregoing discussion relates to bacteria as they 

 occur in nature. Other mechanisms of resistance come into 

 play with resistant variants of naturally sensitive bacteria. 

 Such resistant variants usually bind penicillin to at least 

 the same degree as does the sensitive parent cell, but an 

 ordinarily lethal degree of combination now has no effect 

 on growth and multiplication. Their resistance may there- 

 fore involve one or more mechanisms qualitatively distinct 

 from any of those previously discussed. The importance of 

 similar studies with radioactive streptomycin, chlortetra- 

 cycline, and chloramphenicol requires no elaboration. 



Mode of Acflon 



Perhaps the widest gap in our understanding of the 

 antibiotics relates to their mode of action. For each of the 

 important antibiotics, a number of suggestions have been 

 made, each based on experimental observations. This very 

 multiplicity of theories suggests that none may represent 

 the primary locus of action of the antibiotic. The striking 

 accumulation of uridine phosphates in penicillin-treated 

 bacteria; the puzzling observation that the binding of peni- 

 cillin does not initiate the death of the organisms unless 

 that binding occurs in a medium favorable for growth; 

 the inhibition of adaptive enzyme formation by a number 

 of antibiotics; the elimination of chloroplasts from Euglena 

 by streptomycin, and of the Kappa-factor from paramecia 

 by chloramphenicol; the uncoupling of oxidative phos- 

 phorylation in mammalian tissues by chlortetracycline — 

 these are only a few of the many significant clues from 

 a number of laboratories. But as yet they have not led to 

 a definite explanation for the mode of action of any one 



