Tumescenamide C, a cyclic lipodepsipeptide from Streptomyces sp. KUSC_F05, exerts antimicrobial activity against the scab-forming actinomycete Streptomyces scabiei

J Antibiot (Tokyo). 2024 Jun;77(6):353-364. doi: 10.1038/s41429-024-00716-4. Epub 2024 Mar 25.

Abstract

The antimicrobial activity of tumescenamide C against the scab-forming S. scabiei NBRC13768 was confirmed with a potent IC50 value (1.5 μg/mL). Three tumescenamide C-resistant S. scabiei strains were generated to compare their gene variants. All three resistant strains contained nonsynonymous variants in genes related to cellobiose/cellotriose transport system components; cebF1, cebF2, and cebG2, which are responsible for the production of the phytotoxin thaxtomin A. Decrease in thaxtomin A production and the virulence of the three resistant strains were revealed by the LC/MS analysis and necrosis assay, respectively. Although the nonsynonymous variants were insufficient for identifying the molecular target of tumescenamide C, the cell wall component wall teichoic acid (WTA) was observed to bind significantly to tumescenamide C. Moreover, changes in the WTA contents were detected in the tumescenamide C-resistant strains. These results imply that tumescenamide C targets the cell wall system to exert antimicrobial effects on S. scabiei.

MeSH terms

  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Cell Wall / drug effects
  • Depsipeptides* / chemistry
  • Depsipeptides* / isolation & purification
  • Depsipeptides* / pharmacology
  • Drug Resistance, Bacterial
  • Indoles
  • Microbial Sensitivity Tests
  • Peptides, Cyclic* / chemistry
  • Peptides, Cyclic* / isolation & purification
  • Peptides, Cyclic* / pharmacology
  • Piperazines
  • Streptomyces* / chemistry
  • Streptomyces* / drug effects
  • Streptomyces* / genetics
  • Teichoic Acids / metabolism

Substances

  • Anti-Bacterial Agents
  • Depsipeptides
  • Indoles
  • Peptides, Cyclic
  • Piperazines
  • Teichoic Acids
  • thaxtomine A

Supplementary concepts

  • Streptomyces scabiei