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

The Journal of Antibiotics volume 77, pages 353–364 (2024)Cite this article

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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.

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Data sets generated for this study are included in this article or supporting information; further information can be directed to the corresponding author (H.K.).

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Acknowledgements

This work was supported by a Grant-in Aid for Scientific Research on Innovative Areas (No. 17H06401 to HK) and for the Transformative Research Area (A) (No. 23H04882 to HK) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan, and the Research Support Project for Life Science and Drug Discovery [Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from the Japan Agency for Medical Research and Development (AMED), Japan. This work was also inspired by the international and interdisciplinary environments of JSPS Asian CORE program, “Asian Chemical Biology Initiative”.

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  1. Kensuke Kaneko

    Present address: Hachinohe College of Technology, Aomori, 039-1192, Japan

Authors and Affiliations

  1. Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan

    Kensuke Kaneko, Marika Mieda, Yulu Jiang, Nobuaki Takahashi & Hideaki Kakeya

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Correspondence to Hideaki Kakeya.

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Kaneko, K., Mieda, M., Jiang, Y. et al. Tumescenamide C, a cyclic lipodepsipeptide from Streptomyces sp. KUSC_F05, exerts antimicrobial activity against the scab-forming actinomycete Streptomyces scabiei. J Antibiot 77, 353–364 (2024). https://doi.org/10.1038/s41429-024-00716-4

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