Abstract
The mechanism of action of a new antibiotic, negamycin, was studied in Escherichia coli K12.
1. Negamycin exhibited a bacteriocidal action, and in macromolecular synthesis in negamycin-treated cells inhibition of protein synthesis was first demonstrated and then a decline of RNA synthesis followed with a little delay. The synthesis of DNA and cell wall was hardly impaired. These results indicate that protein synthesis is the primary site of inhibition by negamycin of the growing cells.
2. Negamycin inhibited in vitro protein synthesis directed by phage MS2 RNA as exogenous natural messenger RNA, and when the drug was added at the start of incubation the inhibition was marked during the first 5 or 10 minutes of the incubation and progressively decreased with the time. Furthermore, less inhibition was shown if the drug was added after protein synthesis had begun.
3. On the other hand, in vitro protein synthesis directed by endogenous natural mRNA was not inhibited but was rather stimulated by negamycin.
4. Negamycin inhibited binding of formylated methionyl-tRNA to ribosomes directed by MS2 RNA.
5. From these results negamycin seems to be a specific inhibitor of peptide chain initiation in natural mRNA directed protein synthesis and not of peptide chain elongation.
