Abstract
Mureidomycin A (MRD), a novel peptidylnucleoside antibiotic with antipseudomonal activity, inhibited not only peptidoglycan synthesis but also lipid-intermediate formation from UDP-N-acetylmuramyl (MurNAc)-pentapeptide and UDP-N-acetylglucosamine in an in vitro peptidoglycan-synthesizing system, using ether-treated cells of Pseudomonas aeruginosa. Both types of inhibition by MRD disappeared when UDP-MurNAc-pentapeptide was preincubated with ether-treated cells. Moreover, MRD completely inhibited lipid-intermediate I (undecaprenyl-p-p-MurNAc-pentapeptide) formation at a concentration below the MIC. From these results, it was concluded that the real target of MRD's action was translocase, which catalyzes lipid-intermediate I formation from UDP-MurNAc-pentapeptide and a lipid carrier.
Full text
PDF


Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allen N. E., Hobbs J. N., Alborn W. E., Jr Inhibition of peptidoglycan biosynthesis in gram-positive bacteria by LY146032. Antimicrob Agents Chemother. 1987 Jul;31(7):1093–1099. doi: 10.1128/aac.31.7.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hammes W. P., Neuhaus F. C. On the mechanism of action of vancomycin: inhibition of peptidoglycan synthesis in Gaffkya homari. Antimicrob Agents Chemother. 1974 Dec;6(6):722–728. doi: 10.1128/aac.6.6.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inukai M., Isono F., Takahashi S., Enokita R., Sakaida Y., Haneishi T. Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. I. Taxonomy, fermentation, isolation and physico-chemical properties. J Antibiot (Tokyo) 1989 May;42(5):662–666. doi: 10.7164/antibiotics.42.662. [DOI] [PubMed] [Google Scholar]
- Isono F., Inukai M., Takahashi S., Haneishi T., Kinoshita T., Kuwano H. Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. II. Structural elucidation. J Antibiot (Tokyo) 1989 May;42(5):667–673. doi: 10.7164/antibiotics.42.667. [DOI] [PubMed] [Google Scholar]
- Isono F., Katayama T., Inukai M., Haneishi T. Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. III. Biological properties. J Antibiot (Tokyo) 1989 May;42(5):674–679. doi: 10.7164/antibiotics.42.674. [DOI] [PubMed] [Google Scholar]
- Kang M. S., Spencer J. P., Elbein A. D. Amphomycin inhibits the incorporation of mannose and GlcNAc into lipid-linked saccharides by aorta extracts. Biochem Biophys Res Commun. 1978 May 30;82(2):568–574. doi: 10.1016/0006-291x(78)90912-9. [DOI] [PubMed] [Google Scholar]
- Lugtenberg E. J., de Haan P. G. A simple method for following the fate of alanine-containing components in murein synthesis in Escherichia coli. Antonie Van Leeuwenhoek. 1971;37(4):537–552. doi: 10.1007/BF02218524. [DOI] [PubMed] [Google Scholar]
- Mirelman D., Nuchamowitz Y. Biosynthesis of peptidoglycan in Pseudomonas aeruginosa. 1. The incorporation of peptidoglycan into the cell wall. Eur J Biochem. 1979 Mar;94(2):541–548. doi: 10.1111/j.1432-1033.1979.tb12923.x. [DOI] [PubMed] [Google Scholar]
- Mirelman D., Nuchamowitz Y. Biosynthesis of peptidoglycan in Pseudomonas aeruginosa. 2. Mode of action of beta-lactam antibiotics. Eur J Biochem. 1979 Mar;94(2):549–556. doi: 10.1111/j.1432-1033.1979.tb12924.x. [DOI] [PubMed] [Google Scholar]
- Oka T. Mode of action of penicillins in vivo and in vitro in Bacillus megaterium. Antimicrob Agents Chemother. 1976 Oct;10(4):579–591. doi: 10.1128/aac.10.4.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- STRUVE W. G., NEUHAUS F. C. EVIDENCE FOR AN INITIAL ACCEPTOR OF UDP-NAC-MURAMYL-PENTAPEPTIDE IN THE SYNTHESIS OF BACTERIAL MUCOPEPTIDE. Biochem Biophys Res Commun. 1965 Jan 4;18:6–12. doi: 10.1016/0006-291x(65)90873-9. [DOI] [PubMed] [Google Scholar]
- Siewert G., Strominger J. L. Bacitracin: an inhibitor of the dephosphorylation of lipid pyrophosphate, an intermediate in the biosynthesis of the peptidoglycan of bacterial cell walls. Proc Natl Acad Sci U S A. 1967 Mar;57(3):767–773. doi: 10.1073/pnas.57.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strominger J. L., Willoughby E., Kamiryo T., Blumberg P. M., Yocum R. R. Penicillin-sensitive enzymes and penicillin-binding components in bacterial cells. Ann N Y Acad Sci. 1974 May 10;235(0):210–224. doi: 10.1111/j.1749-6632.1974.tb43267.x. [DOI] [PubMed] [Google Scholar]
- Tanaka H., Oiwa R., Matsukura S., Omura S. Amphomycin inhibits phospho-N-acetylmuramyl-pentapeptide translocase in peptidoglycan synthesis of Bacillus. Biochem Biophys Res Commun. 1979 Feb 14;86(3):902–908. doi: 10.1016/0006-291x(79)91797-2. [DOI] [PubMed] [Google Scholar]
- Vosberg H. P., Hoffmann-Berling H. DNA synthesis in nucleotide-permeable Escherichia coli cells. I. Preparation and properties of ether-treated cells. J Mol Biol. 1971 Jun 28;58(3):739–753. doi: 10.1016/0022-2836(71)90037-4. [DOI] [PubMed] [Google Scholar]
- Ward J. B. Tunicamycin inhibition of bacterial wall polymer synthesis. FEBS Lett. 1977;78(1):151–154. doi: 10.1016/0014-5793(77)80294-9. [DOI] [PubMed] [Google Scholar]