Studies on a new antibiotic M-92 produced by micromonospora. V. Mechanism of action of the component VA-2.
Effects of VA-2, a component of quinoid antibiotic M-92, on the incorporation of radioisotope-labeled compounds into the cells of Staphylococcus aureus were studied. Deoxyribonucleic acid (DNA) synthesis was immediately inhibited by the addition of VA-2. Significant inhibitions of ribonucleic acid and protein syntheses and minor reduction of peptidoglycan synthesis were observed after a short delay. VA-2 immediately induced the degradation of DNA prelabelled with [14C]thymidine in the cells of S. aureus. In the examinations using E. coli enzyme and calf thymus DNA as a template, VA-2 prevented DNA-dependent DNA polymerase reaction. The inhibition of DNA polymerase I reaction was fairly reversed by increasing the concentration of template DNA, but slightly by that of the enzyme. Agarose gel electrophoresis showed that VA-2 elicited an extensive cleavage of PM2 cccDNA. VA-2 caused a primary conversion of the cccDNA to ocDNA at a low concentration (0.2 micrograms/ml), while at high concentrations (2.0 and 20 micrograms/ml) it cleaved the cccDNA to ocDNA and linear DNA progressively. These cleavages were observed even at 0 degrees C as well as at 37 degrees C, and were enhanced with the addition of a reducing agent such as 2-mercaptoethanol or sodium borohydride.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D001435:Bacteriophages / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D008847:Micromonospora / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors; D013211:Staphylococcus aureus / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D009285:Naphthoquinones; D019384:Nucleic Acid Synthesis Inhibitors; C036968:M 92