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Journal of Bacteriology, January 2002, p. 18-28, Vol. 184, No. 1
0021-9193/01/$04.00+0     DOI: 10.1128/JB.184.1.18-28.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Trypsin Mediates Growth Phase-Dependent Transcriptional Regulation of Genes Involved in Biosynthesis of Ruminococcin A, a Lantibiotic Produced by a Ruminococcus gnavus Strain from a Human Intestinal Microbiota

Ana Gomez,* Monique Ladiré, Françoise Marcille, and Michel Fons

Unité d’Ecologie et Physiologie du Système Digestif, Institut National de la Recherche Agronomique, Centre de Recherches de Jouy en Josas, F-78352 Jouy en Josas Cedex, France

Received 9 July 2001/ Accepted 2 October 2001

Ruminococcin A (RumA) is a trypsin-dependent lantibiotic produced by Ruminococcus gnavus E1, a gram-positive strict anaerobic strain isolated from a human intestinal microbiota. A 12.8-kb region from R. gnavus E1 chromosome, containing the biosynthetic gene cluster of RumA, has been cloned and sequenced. It consisted of 13 open reading frames, organized in three operons with predicted functions in lantibiotic biosynthesis, signal transduction regulation, and immunity. One unusual feature of the locus is the presence of three almost identical structural genes, all of them encoding the RumA precursor. In order to determine the role of trypsin in RumA production, the transcription of the rum genes has been investigated under inducing and noninducing conditions. Trypsin activity is needed for the growth phase-dependent transcriptional activation of RumA operons. Our results suggest that bacteriocin production by R. gnavus E1 is controlled through a complex signaling mechanism involving the proteolytic processing of a putative extracellular inducer-peptide by trypsin, a specific environmental cue of the digestive ecosystem.

* Corresponding author. Mailing address: UEPSD, Bâtiment 440-R2, CRJ-INRA, F-78352 Jouy en Josas Cedex, France. Phone: (33) 1-34-65-24-69. Fax: (33) 1-34-65-24-62. E-mail: gomez{at}jouy.inra.fr.

Journal of Bacteriology, January 2002, p. 18-28, Vol. 184, No. 1
0021-9193/01/$04.00+0     DOI: 10.1128/JB.184.1.18-28.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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