title: Salivaricin 9, a new lantibiotic produced by Streptococcus salivarius.
abstract: Salivaricin 9 (Sal9) is a 2560 Da lantibiotic having just 46 % amino acid identity with its closest known homologue, the Streptococcus pyogenes lantibiotic SA-FF22. The Sal9 locus (designated siv) in Streptococcus salivarius strain 9 was partially sequenced and localized to an approximately 170 kb megaplasmid, which also harbours the locus for the lantibiotic salivaricin A4. The entire locus was fully characterized in the draft genome sequence of S. salivarius strain JIM8780 and shown to consist of eight genes, having the following putative functions: sivK, sensor kinase; sivR, response regulator; sivA, Sal9 precursor peptide; sivM, lantibiotic modification enzyme; sivT, ABC transporter involved in the export of Sal9 and concomitant cleavage of its leader peptide; and sivFEG, encoding lantibiotic self-immunity. Intriguingly, in contrast to strain 9, the siv locus was chromosomally located in strain JIM8780--the first lantibiotic locus shown not to be exclusively plasmid-associated in S. salivarius. Sal9-containing extracts specifically induced lantibiotic production in both strain 9 and strain JIM8780, indicating that Sal9 functions as a signal peptide for upregulation of its own biosynthesis. Screening representative strains of three streptococcal species (S. salivarius, S. pyogenes and S. mitis) for sivA indicated that it was present only in S. salivarius, with 12 of 28 tested S. salivarius positive. Since Sal9 was inhibitory to all tested S. pyogenes strains it appears to have potential as an important component of the bacteriocin armoury of S. salivarius probiotics intended to control S. pyogenes infections of the human oral cavity.
authors.affiliation: BLIS Technologies Ltd, Dunedin, New Zealand.
authors.forename: P A
authors.initials: PA
authors.lastname: Wescombe
authors.affiliation: Medical Microbiology, School of Translational Medicine, University of Manchester, Clinical Sciences Building, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
authors.forename: M
authors.initials: M
authors.lastname: Upton
authors.affiliation: Genetique Microbienne, INRA-CRJ, 78352 Jouy en Josas Cedex, France.
authors.forename: P
authors.initials: P
authors.lastname: Renault
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: R E
authors.initials: RE
authors.lastname: Wirawan
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: D
authors.initials: D
authors.lastname: Power
authors.affiliation: BLIS Technologies Ltd, Dunedin, New Zealand.
authors.forename: J P
authors.initials: JP
authors.lastname: Burton
authors.affiliation: BLIS Technologies Ltd, Dunedin, New Zealand.
authors.forename: C N
authors.initials: CN
authors.lastname: Chilcott
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: J R
authors.initials: JR
authors.lastname: Tagg
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D016415:Sequence Alignment; D013291:Streptococcus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D021382:Protein Sorting Signals