Streptococcus uberis is one of the principal causative agents of bovine mastitis. In this study, we report that S. uberis strain 42 produces a lantibiotic, nisin U, which is 78% identical (82% similar) to nisin A from Lactococcus lactis. The 15.6-kb nisin U locus comprises 11 open reading frames, similar in putative functionality but differing in arrangement from that of the nisin A biosynthetic cluster. The nisin U producer strain exhibits specific resistance (immunity) to nisin U and cross-resistance to nisin A, a finding consistent with the 55% sequence similarity of their respective immunity peptides. Homologues of the nisin U structural gene were identified in several additional S. uberis strains, and in each case cross-protective immunity was expressed to nisin A and to the other producers of nisin U and its variants. To our knowledge, this is the first report both of characterization of a bacteriocin by S. uberis, as well as of a member of the nisin family of peptides in a species other than L. lactis.The lactic acid bacterium Streptococcus uberis, in nature primarily found on the lips and skin of cows, in raw milk, and on udder tissue (11), is also a major cause of bovine mastitis (4). Due to the ubiquity of this bacterium in the environment of the dairy cow, teat-end contamination poses a constant threat of infection, and the current level of disease caused by S. uberis remains a persistent problem impacting both on the economic production of milk and on the welfare of the dairy cow (21).Many lactic acid bacteria produce broad-spectrum proteinaceous antimicrobials called bacteriocins, some of which could provide valuable alternatives to traditional therapeutic antibiotics for the treatment of infectious diseases (30). Two such bacteriocins, nisin and lacticin 3147, which are produced by strains of Lactococcus lactis are potential candidates for mastitis control (5, 30). Nisin is the active ingredient in two commercial products: Consept (Applied Microbiology, Inc., New York, NY) and Wipe-Out (ImmuCell, Portland, OR). Lacticin 3147 has also been evaluated as a teat-seal formulation for the prevention of mastitis during the "dry" period in which the cow is not lactating (30).Nisin and lacticin 3147 both belong to the lantibiotic class of bacteriocins (10, 34). The lantibiotics are ribosomally synthesized, low-molecular-weight, heat-stable peptides characterized by their content of posttranslationally modified amino acids, including lanthionine and/or ␤-methyl-lanthionine (22,26,31). Nisin is the most intensively studied lantibiotic (20,35,37). Nisin Z (25) and nisin Q (45) are two natural variants of the original nisin A, differing in their propeptide components from nisin A by one and four amino acids, respectively. Lantibiotic loci typically comprise a structural gene (lanA) and other genes that encode proteins responsible for posttranslational modification of the prepeptide (lanB and lanC, or lanM), proteolytic processing (lanP), transport (lanT), producer selfprotection (lanI and lanEFG), and regulatio...

Streptococcus salivarius strains commonly produce bacteriocins as putative anti-competitor or signalling molecules. Here we report that bacteriocin production by the oral probiotic strain S. salivarius K12 is encoded by a large (ca. 190 kb) plasmid. Oral cavity transmission of the plasmid from strain K12 to a plasmid-negative variant of this bacterium was demonstrated in two subjects. Tests of additional S. salivarius strains showed large (up to ca. 220 kb) plasmids present in bacteriocin-producing isolates. Various combinations (up to 3 per plasmid) of loci encoding the known streptococcal lantibiotics salivaricin A, salivaricin B, streptin and SA-FF22 were localised to these plasmids. Since all bacteriocin-producing strains of S. salivarius tested to date appear to harbour plasmids, it appears that they may function as mobile repositories for bacteriocin loci, especially those of the lantibiotic class.

Streptococcus mutans strain K8 was shown to produce a newly identified type AII lantibiotic, mutacin K8. The mutacin K8-encoding muk locus consists of 13 ORFs, three of which (mukA1, A2 and A3) have close homology to scnA, the structural gene encoding the Streptococcus pyogenes lantibiotic SA-FF22, and another (mukA9) resembles scnA9, an ORF in the SA-FF22 locus that has no currently assigned function. Inactivation of the muk locus indicated that mutacin K8 is responsible for most of the inhibitory activity produced by strain K8 in deferred antagonism tests on Columbia blood agar base supplemented with 5 % human blood and 0.1 % CaCO 3 . By contrast, on tryptic soy agar plus 2 % yeast extract and 0.5 % CaCO 3 most of the inhibitory activity of strain K8 appeared to be attributable either to mutacin IV or to some other inhibitory peptide(s) exported by the mutacin IV transporter nlmT. An inhibitory peptide purified from a derivative of strain K8 in which nlmT had been inactivated had a mass of 2734 Da and an N-terminal sequence identical to the predicted propeptide translation products of mukA1 and mukA3. The muk locus may be widely distributed in S. mutans, since 9 (35 %) of 26 strains tested contained at least part of the locus. In the genome sequence of strain UA159 the muk locus is incomplete, the sole residual components being the ORFs encoding the putative two-component regulatory system mukR (SMU.1815) and mukK (SMU.1814), followed by two transposases (SMU.1813 and SMU.1812) and then the ORFs mukF (SMU.1811), mukE (SMU.1810) and mukG (SMU.1809), thought to encode putative immunity peptides. Strains such as UA159 having incomplete loci did not produce detectable levels of mutacin K8.