Growth and Initiation of Protein Synthesis inEscherichia coliin the Presence of Trimethoprim

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Abstract
Escherichia coligrew exponentially at a reduced rate in the presence of 50 or 100 μg of trimethoprim/ml if the low-molecular-weight products of folate metabolism or their precursors (thymidine, purines, methionine, glycine, and pantothenate) were supplied in the medium. Folate metabolism was inhibited 99.9% by these concentrations of trimethoprim, but a low level of formylation of methionyl transfer ribonucleic acid (met-tRNAF) could be detected. However, in a medium containing all major amino acids, nucleosides, and vitamins, formylation of met-tRNAFwas undetectable in the presence of trimethoprim. No other amino-masked amino acids were detected, and methionine remained a major amino-terminal amino acid of mature proteins. met-tRNAFwas rapidly labeled with exogenous methionine and was associated with 30sribosomal subunits and 70sribosomes. It was concluded that initiation of protein synthesis can occur with unformylated met-tRNAFinE. coli. Changes in macromolecular composition were associated with the lack of formylation, in particular a fourfold increase in both met-tRNAFand ribosomal subunits. These changes would tend to compensate for the low specific rate of initiation with unformylated met-tRNAF.