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Micrococcins from Peribacillus sp. KDM594; efficacy against vancomycin-resistant enterococci and drug metabolism in a silkworm model

The Journal of Antibiotics volume 78, pages 481–487 (2025)Cite this article

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Abstract

The screening of antibiotics derived from microbial resources to combat vancomycin-resistant enterococci (VRE) revealed that a culture of marine-derived Peribacillus sp. KDM594 exhibited significant therapeutic efficacy in an infected in vivo-mimic silkworm model. Bioassay-guided purification led to the isolation of micrococcins P1 (1) and P2 (2), which exhibited potent antimicrobial activities against Gram-positive bacteria, including VRE, methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium spp., with MIC values ranging from 0.25 to 8.0 µg ml−1 using the microdilution method. In the silkworm models infected with VRE or MRSA, 1 and 2 exerted moderate therapeutic effects, with ED50 values ranging from 3.2 to 51 µg larva−1 g−1. Furthermore, a pharmacokinetic analysis revealed that 2 was metabolized to 1 in the silkworm hemolymph, and their elimination half-lives were 3.2 and 3.0 h, respectively. These results suggest that micrococcins are promising lead compounds for the development of anti-VRE and MRSA drugs.

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Authors and Affiliations

  1. Division of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan

    Akiho Yagi, Mayu Sato & Ryuji Uchida

  2. Department of Fisheries, Faculty of Agriculture, Kindai University, Nara, Japan

    Katsuki Kikuchi, Akito Taniguchi & Takashi Fukuda

  3. Agricultural Technology and Innovation Research Institute, Kindai University, Nara, Japan

    Takashi Fukuda

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  1. Akiho Yagi
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Correspondence to Akiho Yagi or Ryuji Uchida.

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Yagi, A., Sato, M., Kikuchi, K. et al. Micrococcins from Peribacillus sp. KDM594; efficacy against vancomycin-resistant enterococci and drug metabolism in a silkworm model. J Antibiot 78, 481–487 (2025). https://doi.org/10.1038/s41429-025-00838-3

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