Inhibition of Microbial Cell Wall Synthesis by Lipopeptin A

Abstract

Lipopeptin A is a selective inhibitor of in vitro peptidoglycan synthesis of E. coli Y-10. In the study here it inhibited the formation of lipid intermediates from UDP-[U-¹⁴C]GlcNAc and UDP-MurNAc- L-Ala-D-Glu-meso-DAP-D-Ala-D-Ala, but did not inhibit the formation of MurNAc-pentapeptide-p-p-lipid from UDP-MurNAc-L-Ala-D-Glu-[³H]meso-DAP-D-Ala-D-Ala. Lipopeptin A also did not have a significant effect on polymerase reaction. Therefore, the inhibition of the formation of GlcNAc-MurNAc-pentapeptide-p-p-lipid from MurNAc-pentapeptide-p-p-lipid and UDP-GlcNAc is concluded to be the site of action.
Lipopeptin A inhibits fungal growth, causing swelling in mycelia. It did not significantly inhibit the incorporations of ¹⁴C-labeled glucosamine, thymidine, uridine, phenylalanine, and sodium acetate into TCA insoluble fraction of mycelial suspension of Piricularia oryzae. In in vitro test, however, it inhibited the transfer of mannose from GDP-[U-¹⁴C]mannose (ID₅₀ =250 μg/ml) and GlcNAc from UDP-[U-¹⁴C]GlcNAc (ID₅₀ = 100 μg/ml) into proteoheteroglycan with a particulate enzyme of Piricularia oryzae. It also slightly inhibited chitin synthesis (ID₅₀ = 750 μg/ml) in the same enzyme system, but did not inhibit β-l, 3-glucan synthesis.