Cycloimidamicins, Novel natural lead compounds for translation inhibition in Pseudomonas aeruginosa

J Antibiot (Tokyo). 2023 Dec;76(12):691-698. doi: 10.1038/s41429-023-00656-5. Epub 2023 Sep 27.

Abstract

Pseudomonas aeruginosa is one of the most concerning pathogenic bacteria. We screened antibiotics using a highly drug-sensitive P. aeruginosa strain and an oligotrophic medium, and successfully isolated novel antibiotics, namely cycloimidamicins (CIMs), from a rare actinomycete strain, Lentzea sp. MM249-143F7. X-ray and nuclear magnetic resonance analyses revealed that CIMs possess a distinctive and unprecedented molecular structure, containing tetramic acid and an imidazole ring bound directly to indolone. The CIMs exhibited potent antibacterial activity against Gram-negative bacteria, as well as translation inhibition in Escherichia coli in both intact cells and in vitro. Additionally, E. coli strains resistant to known translation inhibitors did not exhibit cross-resistance to CIMs, suggesting that CIMs inhibit bacterial growth by blocking translation through a novel mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacteria
  • Escherichia coli*
  • Gram-Negative Bacteria
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa*

Substances

  • Anti-Bacterial Agents