The mechanism of action of polychlorosubtilin.

Polychlorosubtilin (PCS) inhibits the growth of Escherichia coli. The antibiotic affected neither respiration nor glycolysis while the synthesis of nucleic acids and proteins were feebly hindered. Formation of aminoacyl-tRNA, peptide bonds and translocation from A to P sites of ribosomes were insignificantly influenced by the drug. The antibiotic exerted its effect(s) on ribosomes by interfering with the 30 S subunits. The 23 S and 30 SP were both sensitive to the drug but the latter was more obviously affected. Changes after developing resistance to the drug by the bacteria were localized in the 30 SP, 23 S and accordingly the 30 S subunits. The principal action of PCS was to cause multisited miscoding upon the incorporation of labeled aminoacyl-tRNA, therefore, malformed protein fractions (abnormal) were synthesized. As a natural consequence such abnormal fractions would not be expected to manifest the vital metabolic activities in the normal way.