Inhibition by Chloramphenicol of Glucose Transfer in Teichoic Acid Biosynthesis

Abstract

CHLORAMPHENICOL is widely accepted as a highly effective inhibitor of protein synthesis in bacteria, both in whole cells and at the subcellular level. Although some of the details of its mechanism of action are still unsettled, it has been shown to bind selectively to the 50S ribosomal subunit¹ and to inhibit peptide formation possibly by preventing binding between the ribosome and raRNA². It is well established that the bacteriostatic action of the antibiotic results from inhibition of protein synthesis, and its use as a tool in the study of cellular biochemistry is frequently based on the view that its action is highly specific. In fact, there are reports of its inhibitory action on other cell processes³, but these are either relatively unimportant or the effects are only shown at concentrations of antibiotic much higher than those required for inhibition of protein synthesis. Anraku and Landman⁴ have reported that chloramphenicol inhibits a late stage in the reversion of protoplasts of Bacillus subtilis to the osmotically stable bacillary form, and this is accompanied by inhibition of synthesis of a phosphorylated wall polymer believed to be a teichoic acid. It was suggested that inhibition of synthesis of wall polymers, including the teichoic acid, was an indirect effect arising from inhibition of synthesis of the appropriate enzyme proteins. We now report that chloramphenicol powerfully inhibits the biosynthesis of a wall teichoic acid in a cell-free system of fragmented cytoplasmic membrane from B. licheniformis ATCC 9945 (B. subtilis NCIB 8062); this occurs through direct action on the teichoic acid synthesizing system and is unrelated to protein synthesis. Although this may provide an alternative explanation of the effect observed by Anraku and Landman, a more detailed study of their system would be required.