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J. Bacteriol. doi:10.1128/JB.00969-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Siamycin attenuates fsr quorum sensing mediated by gelatinase biosynthesis-activating pheromone in Enterococcus faecalis

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

^* To whom correspondence should be addressed. Email: nakayama{at}agr.kyushu-u.ac.jp,

	Abstract

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 for inhibitors of the fsr quorum sensing from actinomycetes metabolites. E. faecalis was cultured with each tested actinomycetes culture supernatant and the productions of gelatinase and GBAP were tested for the first and second screenings, respectively. Culture supernatant of Streptomyces sp. Y33-1 showed the most potent inhibitory effect on both gelatinase and GBAP productions 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 and GBAP productions at submicromolar concentrations, and 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 the 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 FsrC-FsrA two-component regulatory system in a noncompetitive manner. The sublethal concentrations of siamycin I also attenuated biofilm formation. Siamycin would offer a novel means of treating enterococcal infections.