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Furanone derivatives as quorum-sensing antagonists of Pseudomonas aeruginosa

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Abstract

The biofilm formation of Pseudomonas aeruginosa, an opportunistic human pathogen, is developed by cell-to-cell signaling, so-called quorum sensing (QS). To control the biofilm formation, we designed and synthesized new QS inhibitors of P. aeruginosa based on the structure of the previously known QS inhibitor, furanone. Newly synthesized compounds were a series of analogs of (5-oxo-2,5-dihydrofuran-3-yl)methyl alkanoate, and the structures of all six synthesized compounds was confirmed by NMR and GC/MS analyses. These new QS inhibitor candidates could remarkably inhibit both Pseudomonas QS signaling and biofilm formation, which were assayed by using the recombinant reporter system and flow cell confocal microscopy. The degree of QS inhibition by these new inhibitors varied from 20% to 90%. For the profound understanding about inhibition mechanism, we tried to estimate the binding energy between QS receptor, LasR, and our inhibitors from the in silico modeling system. The predicted binding pattern from the modeling system and our experimental data about QS inhibition were in good agreement. From these results, we suggest a new approach to develop the QS inhibitors and biofilm control agents based on structural modeling.

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Acknowledgments

This research was partially supported by the Brain Korea 21 Program (the Ministry of Education). In addition, this work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST; no. R01-2007-000-20732-0). The authors wish to acknowledge the financial support by the Seoul R&D Program (10538) through the Institute of Bioengineering, Seoul National University, Seoul, South Korea. For Joon-Hee Lee, this work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2007-331-C00222).

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Authors and Affiliations

  1. School of Chemical and Biological Engineering, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul, 151-742, South Korea

    Cheoljin Kim, Jaeeun Kim, Hee-Jin Park & Jeyong Yoon

  2. Department of Chemistry, College of Natural Science, Inha University, 253, Yonghyun-dong, Nam-gu, Incheon, 402-751, South Korea

    Hyung-Yeon Park & Chan Kyung Kim

  3. Department of Pharmacy, College of Pharmacy, Pusan National University, Geum Jeong-gu, Busan, 609-735, South Korea

    Joon Hee Lee

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  1. Cheoljin Kim
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  2. Jaeeun Kim
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  3. Hyung-Yeon Park
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  4. Hee-Jin Park
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  5. Joon Hee Lee
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Correspondence to Jeyong Yoon.

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Kim, C., Kim, J., Park, HY. et al. Furanone derivatives as quorum-sensing antagonists of Pseudomonas aeruginosa . Appl Microbiol Biotechnol 80, 37–47 (2008). https://doi.org/10.1007/s00253-008-1474-6

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  • DOI: https://doi.org/10.1007/s00253-008-1474-6

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