In vivo and in vitro action of new antibiotics interfering with the utilization of N-acetyl-glucosamine-N-acetyl-muramyl-pentapeptide.
Recent literature on the antibiotics enduracidin, moenomycin, prasinomycin, and 11.837 RP suggested an interaction with murein synthesis. Incubation of sensitive strains from Bacillus cereus and Staphylococcus aureus in a "wall medium" containing labeled l-alanine showed that all four antibiotics inhibited the incorporation of alanine into murein and gave rise to accumulation of radioactive uridine diphosphate-N-acetyl-muramyl (UDP-MurNAc)-pentapeptide. Peptidoglycan was synthesized when the particulate enzyme of B. stearothermophilus was incubated with the murein precursors UDP-N-acetyl-glucosamine (UDP-GlcNAc) and UDP-MurNAc-pentapeptide. The newly formed polymer was less accessible for lysozyme and more strongly bound to the acceptor than the same product from the Escherichia coli particulate enzyme. After incubation in the presence of penicillin, a greater part of the peptidoglycan was lysozyme sensitive and more loosely bound to the acceptor. The antibiotics enduracidin, moenomycin, prasinomycin, and 11.837 RP inhibited peptidoglycan synthesis by the B. stearothermophilus particulate enzyme. The rate of synthesis of GlcNAc-MurNAc(-pentapeptide)-P-P-phospholipid was independent from the addition of these antibiotics, but its utilization was strongly inhibited. With the present results, it is not possible to distinguish the mechanisms of action of enduracidin, moenomycin, prasinomycin, and 11.837 RP from the mechanisms of action of vancomycin and ristocetin.
D000409:Alanine / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001345:Autoradiography; D001407:Bacillus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D001409:Bacillus cereus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002247:Carbon Isotopes; D002474:Cell-Free System; D002854:Chromatography, Paper; D003470:Culture Media; D004798:Enzymes / Q000302:isolation & purification / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006020:Glycopeptides / Q000378:metabolism; D006358:Hot Temperature; D009113:Muramidase; D010406:Penicillins; D010455:Peptides / Q000378:metabolism*; D010457:Peptidoglycan / Q000096:biosynthesis; D011134:Polysaccharides / Q000378:metabolism*; D013210:Staphylococcus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013237:Stereoisomerism; D013696:Temperature
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002247:Carbon Isotopes; D003470:Culture Media; D004798:Enzymes; D006020:Glycopeptides; D010406:Penicillins; D010455:Peptides; D010457:Peptidoglycan; D011134:Polysaccharides; D009113:Muramidase; D005944:Glucosamine; D000409:Alanine