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Journal of Bacteriology, February 2007, p. 1358-1365, Vol. 189, No. 4
0021-9193/07/$08.00+0     doi:10.1128/JB.00969-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Siamycin Attenuates fsr Quorum Sensing Mediated by a Gelatinase Biosynthesis-Activating Pheromone in Enterococcus faecalis{triangledown}

Jiro Nakayama,1* Emi Tanaka,1 Reiko Kariyama,2 Koji Nagata,3 Kenzo Nishiguchi,1 Ritsuko Mitsuhata,2 Yumi Uemura,1 Masaru Tanokura,3 Hiromi Kumon,2 and Kenji Sonomoto1,4

Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School,1 Department of Functional Metabolic Design, Bio-architecture Center, Kyushu University, Fukuoka 812-8581, Japan,4 Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan,2 Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan3

Received 4 July 2006/ Accepted 9 October 2006

The expression of two Enterococcus faecalis virulence-related proteases, gelatinase (GelE) and serine protease (SprE), is positively regulated by a quorum-sensing system encoded by the fsr gene cluster. In this system, E. faecalis secretes an autoinducing peptide, gelatinase biosynthesis-activating pheromone (GBAP), which triggers the FsrC-FsrA two-component regulatory system controlling the expression of two transcripts, fsrBDC and gelE-sprE. In the present study, we screened actinomycete metabolites for inhibitors of fsr quorum sensing. E. faecalis was cultured with each actinomycete culture supernatant tested, and the production of gelatinase and the production of GBAP were examined using the first screening and the second screening, respectively. Culture supernatant of Streptomyces sp. strain Y33-1 had the most potent inhibitory effect on both gelatinase production and GBAP production without inhibiting E. faecalis cell growth. The inhibitor in the culture supernatant was identified as a known peptide antibiotic, siamycin I. Siamycin I inhibited both gelatinase production and GBAP production at submicromolar concentrations, and it inhibited E. faecalis cell growth at concentrations above micromolar concentrations. Quantitative analysis of fsrBDC and gelE-sprE transcripts revealed that siamycin I suppressed the expression of both transcripts at a sublethal concentration. Siamycin I attenuated gelatinase production even when an overdose of GBAP was exogenously added to the culture. These results suggested that siamycin I inhibited the GBAP signaling via the FsrC-FsrA two-component regulatory system in a noncompetitive manner. The sublethal concentrations of siamycin I also attenuated biofilm formation. Treatment with siamycin could be a novel means of treating enterococcal infections.

* 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 27 October 2006.

Journal of Bacteriology, February 2007, p. 1358-1365, Vol. 189, No. 4
0021-9193/07/$08.00+0     doi:10.1128/JB.00969-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nakayama, J., Uemura, Y., Nishiguchi, K., Yoshimura, N., Igarashi, Y., Sonomoto, K. (2009). Ambuic Acid Inhibits the Biosynthesis of Cyclic Peptide Quormones in Gram-Positive Bacteria. Antimicrob. Agents Chemother. 53: 580-586 [Abstract] [Full Text]  
  • Nishiguchi, K., Nagata, K., Tanokura, M., Sonomoto, K., Nakayama, J. (2009). Structure-Activity Relationship of Gelatinase Biosynthesis-Activating Pheromone of Enterococcus faecalis. J. Bacteriol. 191: 641-650 [Abstract] [Full Text]  


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