AI Article Synopsis

  • - The study focuses on a newly discovered antibiotic, 5812-A/C, derived from the metabolite INA-Ac-5812, which features a cyclic peptide structure linked to an arabinose residue and has a partial amino acid sequence identified.
  • - 5812-A/C is found to have similar inhibitory effects on Gram-positive bacteria, including methicillin-resistant strains, as the lipopeptide antibiotic daptomycin, but it works by disrupting cell membrane integrity differently and is calcium-dependent.
  • - Unlike daptomycin, 5812-A/C can penetrate mature biofilms and has shown weak cytotoxicity, yet it does not cause hemolysis in red blood cells, indicating its potential as a broad

Article Abstract

In this work, we report the isolation and detailed functional characterization for the new non-ribosomally synthesized antibiotic 5812-A/C, which was derived from metabolites of INA-Ac-5812. According to its chemical structure, the studied 5812-A/C preliminary is composed of a cyclic peptide part covalently bounded with an arabinose residue. N-terminal amino acid sequencing of the native peptide has identified its partial structure of Leu-Asp-Gly-Ser-Gly and consisting of a Tyr residue that is supposed to have a two-component peptide nature for the molecule studied. However, the structural analysis of the antibiotic complex derived from INA-Ac-5812 is still ongoing. The mechanism of action of 5812-A/C was assessed in comparison with its most related analog, the lipopeptide antibiotic daptomycin, given the presence in both antimicrobials of an L-kynurenine amino acid residue. The inhibitory activity of 5812-A/C against Gram-positive bacteria including methicillin-resistant strain of was similar to daptomycin. The mechanism of action of 5812-A/C was associated with the disruption of membrane integrity, which differs in comparison with daptomycin and is most similar to the antimicrobial membrane-disturbing peptides. However, 5812-A/C demonstrated a calcium-dependent mode of action. In addition, unlike daptomycin, 5812-A/C was able to penetrate mature biofilms and inhibit the metabolic activity of embedded cells. At the same time, 5812-A/C has no hemolytic activity toward erythrocyte, but possessed weak cytotoxic activity represented by heterochromatin condensation in human buccal epithelium cells. The biological properties of the peptide 5812-A/C suggest its classification as a calcium-dependent antibiotic effective against a wide spectrum of Gram-positive pathogenic bacteria.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533577PMC
http://dx.doi.org/10.3389/fmicb.2020.556063DOI Listing

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Article Synopsis
  • - The study focuses on a newly discovered antibiotic, 5812-A/C, derived from the metabolite INA-Ac-5812, which features a cyclic peptide structure linked to an arabinose residue and has a partial amino acid sequence identified.
  • - 5812-A/C is found to have similar inhibitory effects on Gram-positive bacteria, including methicillin-resistant strains, as the lipopeptide antibiotic daptomycin, but it works by disrupting cell membrane integrity differently and is calcium-dependent.
  • - Unlike daptomycin, 5812-A/C can penetrate mature biofilms and has shown weak cytotoxicity, yet it does not cause hemolysis in red blood cells, indicating its potential as a broad
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