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Spirotetronate antibiotics with anti-Clostridium activity from Actinomadura sp. 2EPS

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Abstract

The rare actinomycetes strain 2EPS was isolated from soil and analysis of cultural, morphological characteristics, diaminopimelic acid content of its cell wall, and 16S rRNA gene sequence indicates that 2EPS belongs to genus Actinomadura. In addition, neighbor-joining phylogenetic tree also confirmed the relationships of this strain to other members of Actinomadura. A butanol extract with antibacterial activity was purified by reversed-phase chromatography to obtain three bioactive compounds, designated as compounds 1, 2 and 3. The structures of these compounds were determined using spectroscopic analysis (1H-NMR and 13C-NMR) and mass spectrometric analysis (HR-TOF-MS). Compounds 1–3 were identified and found to be the same as those included in the Japanese patent number JP 09227587 for spirotetronate antibiotics and are BE-45722A (1), BE-45722B (2) and BE-45722C (3), respectively. All compounds were active against Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 14579, and B. subtilis ATCC 6633) with low MIC values between 0.08 and 5.0 µg/ml. Moreover, both 1 and 3 also exhibited strong activity, with similar MIC values, against Clostridium perfringens S107 at 0.63 µg/ml and C. difficile 630 at 0.08 µg/ml. These results suggest the identified spirotetronate compounds may have potential in the treatment of Clostridium infections. Overall, this analysis demonstrates that rare actinomycetes are a promising source for discovery of antimicrobial compounds.

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Acknowledgments

This study was supported by Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. Ph.D/0103/2552) to JE and WP and by the scholarship from the Japan Student Services Organization (JASSO) to JE. We are grateful to Dr. Laran T. Jensen (Department of Biochemistry, Faculty of Science, Mahidol University) for critically proofreading of the manuscript.

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Authors and Affiliations

  1. Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Jirayut Euanorasetr, Bungonsiri Intra & Watanalai Panbangred

  2. Mahidol University-Osaka University Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Jirayut Euanorasetr, Bungonsiri Intra, Takuya Nihira & Watanalai Panbangred

  3. Department of Biology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Phayungsak Mongkol & Surang Chankhamhaengdecha

  4. Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Patoomratana Tuchinda

  5. Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan

    Mihoko Mori & Kazuro Shiomi

  6. Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan

    Mihoko Mori & Kazuro Shiomi

  7. International Center for Biotechnology, Osaka University, Osaka, Japan

    Takuya Nihira

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  1. Jirayut Euanorasetr
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Correspondence to Watanalai Panbangred.

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Euanorasetr, J., Intra, B., Mongkol, P. et al. Spirotetronate antibiotics with anti-Clostridium activity from Actinomadura sp. 2EPS. World J Microbiol Biotechnol 31, 391–398 (2015). https://doi.org/10.1007/s11274-014-1792-z

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