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Antimicrobial Agents and Chemotherapy, February 2009, p. 580-586, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00995-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ambuic Acid Inhibits the Biosynthesis of Cyclic Peptide Quormones in Gram-Positive Bacteria {triangledown}

Jiro Nakayama,1* Yumi Uemura,1 Kenzo Nishiguchi,1 Norito Yoshimura,1 Yasuhiro Igarashi,2 and Kenji Sonomoto1,3

Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan,1 Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan,2 Department of Functional Metabolic Design, Bio-Architecture Center, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan3

Received 25 July 2008/ Returned for modification 1 October 2008/ Accepted 12 November 2008

Quorum sensing is a cell-density-dependent regulatory system in gram-positive bacteria and is often regulated by cyclic peptides called "quormones," which function as extracellular communication signals. With an aim to discover an antipathogenic agent targeting quorum sensing in gram-positive bacteria, we screened 153 samples of fungal butanol extracts with the guidance of the inhibition of quorum-sensing-mediated gelatinase production in Enterococcus faecalis. Following the screenings, we found that ambuic acid, a known secondary fungal metabolite, inhibited the quorum-sensing-mediated gelatinase production without influencing the growth of E. faecalis. We further demonstrated that ambuic acid targeted the biosynthesis of a cyclic peptide quormone called gelatinase biosynthesis-activating pheromone. Furthermore, ambuic acid also inhibited the biosynthesis of the cyclic peptide quormones of Staphylococcus aureus and Listeria innocua. These results suggest the potential use of ambuic acid as a lead compound of antipathogenic drugs that target the quorum-sensing-mediated virulence expression of gram-positive bacteria.


* Corresponding author. Mailing address: Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. Phone: 81-92-642-3020. Fax: 81-92-642-3021. E-mail: nakayama{at}agr.kyushu-u.ac.jp

{triangledown} Published ahead of print on 17 November 2008.


Antimicrobial Agents and Chemotherapy, February 2009, p. 580-586, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00995-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.