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Lantibiotics produced by lactic acid bacteria: structure, function and applications

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Abstract

Lantibiotics are a diverse group of heavily modified antimicrobial and/or signalling peptides produced by a wide range of bacteria, including a variety of lactic acid bacteria. Based on their diverse structures and mode of action, at least six separate lantibiotic subgroups can be suggested, but all subgroups are characterized by significant post-translational modifications, which include the formation of (β-methyl)lanthionines, among other unusual alterations. These small peptides are produced, modified, exported, sensed and combated by a complex set of proteins encoded by (usually) co-ordinately regulated operons. In some instances, the production and immunity have been shown to be auto-regulated by the mature lantibiotic. Since their discovery, interest in lantibiotics has been fuelled by their obvious potential as food-grade antimicrobials to improve food safety and quality; a potential which, to date, has been realised only by the longest characterised molecule, nisin. In addition, these peptides are often mooted as alternatives to antibiotics for some biomedical applications. The purpose of this paper is to review recent developments in our understanding of lantibiotic structure, molecular genetics and applications for this unusual class of bacteriocins.

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References

  • Abel T& Maniatis T (1989) Gene regulation. Action of leucine zippers. Nature 341: 24–25.

    Google Scholar 

  • Augustin J, Rosenstein R, Wieland B, Schneider U, Schnell N, Engelke G, Entian K-D& Götz F (1992) Genetic analysis of biosynthetic genes and epidermin-negative mutants of Staphylococcus epidermidis. Eur. J. Biochem. 204: 1149–1154.

    Google Scholar 

  • Benz R, Jung G& Sahl H-G (1991) Mechanism of channel-forming lantibiotics in black lipid membranes. In: Jung G& Sahl, HG (Eds) Nisin and Novel Lantibiotics (pp 359–372) ESCOM, Leiden, The Netherlands.

    Google Scholar 

  • Booth MC, Bogie CP, Sahl H-G, Siezen RJ, Hatter KL& Gilmore MS (1996) Structural analysis and proteolytic activation of Enterococcus faecalis cytolysin, a novel lantibiotic. Mol. Microbiol. 21: 1175–1184.

    Google Scholar 

  • Breukink E, van Kraaij C, Demel RA, Siezen RJ, Kuipers OP& de Kruijff B (1997) The C-terminal region of nisin is responsible for the initial interaction of nisin with the target membrane. Biochemistry 36: 6968–6976.

    Google Scholar 

  • Breukink E, Wiedemann I, van Kraaij C, Kuipers OP, Sahl H-G& de Kruijff B (1999) Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 286: 2361–2364.

    Google Scholar 

  • Brotz H, Bierbaum G, Markus A, Molitor E.& Sahl H-G (1995) Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism. Antimicrob. Agents Chemother. 39: 714–719.

    Google Scholar 

  • Brotz H, Bierbaum G, Reynolds PE& Sahl H-G (1997) The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation. Eur. J. Biochem. 246: 193–199.

    Google Scholar 

  • Brotz H, Josten M, Wiedemann I, Schneider U, Gotz F, Bierbaum G& Sahl H-G (1998) Role of lipid-bound peptidoglycan precursors in the formation of pores by nisin, epidermin and other lantibiotics. Mol. Microbiol. 30: 317–327.

    Google Scholar 

  • Coakley M, Fitzgerald G, Ross RP, (1997) Application and evaluation of the phage resistance and bacteriocin encoding plasmid pMRC01 for the improvement of dairy starter cultures. Appl. Environ. Microbiol. 63: 1434–1440.

    Google Scholar 

  • Chan WC, Bycroft BW, Lian L-Y& Roberts GCK (1989) Isolation and characterization of two degradation products derived from the peptide antibiotic nisin. FEBS Lett. 252: 29–36.

    Google Scholar 

  • Chan WC, Dodd HM, Horn N, Maclean K, Lian L-Y, Bycroft BW, Gasson MJ& Roberts GCK (1996) Structure-activity relationships in the peptide antibiotic nisin: role of dehydroalanine 5. Appl. Environ. Microbiol. 62: 2966–2969.

    Google Scholar 

  • Chen P, Qi F, Novak J& Caufield PW (1999) The specific genes for lantibiotic mutacin II biosynthesis in Streptococcus mutans T8 are clustered and can be transferred en bloc. Appl. Environ. Microbiol. 65: 1356–1360.

    Google Scholar 

  • Chinkindas ML, Novak J, Driessen AJM, Konings WN, Schilling KM& Caulfield PW(1995) Mutacin II, a bactericidal lantibiotib form Streptococcus mutans Antimicrobiol. Agents Chemother. 39: 2656–2660.

    Google Scholar 

  • Chow JW, Thal LA, Perri MB, Vasquez JA, Donabedian SM, Clewell DB& Zervos MJ (1993) Plasmid-associated haemolysin and aggregation substance production contributes to virulence in experimental enterococcal endocarditis. Antimicrob. Agents Chemother. 37: 2474–2477.

    Google Scholar 

  • Coburn PS, Hancock LE, Booth MC& Gilmore MS (1999) A novel means of self-protection unrelated to the bactericidal effects of the Enterococcus faecalis cytolysin. Infect. Immun. 67: 3339–3347.

    Google Scholar 

  • Dabard J, Bridonneau C, Phillipe C, Anglade P, Molle D, Nardi M, Ladiré M, Girardin H, Marcille F, Gomez A& Fons M (2001) Ruminococcin A, a new lantibiotic produced by a Ruminococcus gnavus strain isolated form human faeces. Appl. Environ. Microbiol. 67: 4111–4118.

    Google Scholar 

  • de Ruyter PGGA, Kuipers OP& de Vos WM (1996) Controlled gene expression systems for Lactococcus lactis with the foodgrade inducer nisin. Appl. Environ. Microbiol. 62: 3662–3667.

    Google Scholar 

  • de Vos WM, Kuipers OP, van der Meer JR& Siezen RJ (1995) Maturation pathway of nisin and other lantibiotics: post-translationally modified antimicrobial peptides exported by gram-positive bacteria. Mol. Microbiol. 17: 427–437.

    Google Scholar 

  • Delves-Broughton J (1990) Nisin and its uses as a food preservative. Food Tech. 44: 100–117.

    Google Scholar 

  • Delves-Broughton J, Blackburn P, Evans RJ, Hugenholtz J (1996) Applications of the bacteriocin, nisin. Antonie Van Leeuwenhoek 2: 193–202.

    Google Scholar 

  • Diep DB, Hävarstein LS, Nissen-Meyer J& Nes IF (1994) The gene encoding plantaricin A, a bacteriocin from Lactobacillus plantarum C11, is located on the same transcription unit as an agr-like regulatory element. Appl. Environ. Microbiol. 60: 160–166.

    Google Scholar 

  • Dodd HM, Horn N, Chan WC, Giffard CJ, Bycroft BW, Roberts GCK& Gasson MJ (1996) Molecular analysis of the regulation of nisin immunity. Microbiology 142: 2385–2392.

    Google Scholar 

  • Dougherty BA, Hill C, Weidman JF, Richardson DR, Venter JC& Ross RP (1998) Sequence and analysis of the 60 kb conjugative, bacteriocin-producing plasmid pMRC01 from Lactococcus lactis DPC3147. Mol. Microbiol. 29: 1029–1038.

    Google Scholar 

  • Dufour A, Rincé A, Uguen P& le Pennec J-P (2000) IS1675, a novel lactococcal insertion element, forms a transposon-like structure including the lacticin 481 lantibiotic operon. J. Bacteriol. 182: 5600–5605.

    Google Scholar 

  • EEC (1983) EEC Commission Directive 83/463/EEC.

  • Engelke G, Gutowski-Eckel Z, Hammelmann M.& Entian K-D (1992) Biosynthesis of the lantibiotic nisin: genomic organization and membrane localization of the NisB protein. Appl. Environ. Microbiol. 58: 3730–3743.

    Google Scholar 

  • Ferretti JJ, McShan WM, Adjic D, Savic D, Savic G, Lyon K, Primeaux C, Sezate SS, Surorov AN, Kenton S, Lai H, Lin S, Qian Y, Jia HG, Najar FZ, Ren Q, Zhu H, Song L, White J, Yuan X, Clifton SW, Roe BA& McLaughlin RE (2001) Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc. Natl. Acad. Sci. U.S.A. 98: 4658–4663.

    Google Scholar 

  • Freund S, Jung, G, Gibbons WA,& Sahl H-G (1991) NMR and circular dichroism studies on Pep5. In: Sahl H-G,& Jung, J, (Eds) Nisin and Novel Lantibiotics (pp 103–112). ESCOM Scientific Publishers BV, Leiden.

    Google Scholar 

  • Froseth BR& McKay LL (1991) Molecular characterisation of the nisin resistance region of Lactococcus lactis subsp. lactis DRC3. Appl. Environ. Microbiol. 54: 2636–2639.

    Google Scholar 

  • Galvin M, Hill C, Ross RP (1999) Lacticin 3147 displays activity in buffer against Gram-positive bacterial pathogens which appear insensitive in standard plate assays. Lett. Appl. Microbiol. 28: 355–358.

    Google Scholar 

  • Geissler S, Götz F& Kupke T (1996) Serine protease EpiP from Staphylococcus epidermidis catalyses the processing of the epidermin precursor peptide. J. Bacteriol. 178: 284–288.

    Google Scholar 

  • Gilmore MS, Segarra RA, Booth MC, Bogie, CP, Hall, LR& Clewell DB (1994) Genetic structure of the Enterococcus faecalis plasmid pAD1-encoded cytolytic toxin system and its relationship to lantibiotic determinants. J. Bacteriol. 176: 7335–7344.

    Google Scholar 

  • Gomez A, Ladiré M, Marcille F& Fons M (2002) Trypsin mediates growth phase-dependent transcritional regulation of genes involved in biosynthesis of Ruminococcin A, a lantibiotic produced by a Ruminococcus gnavus strain from a human intestinal microbiota. J Bacteriol. 184: 18–28.

    Google Scholar 

  • Gonzalez B, Glaasker E, Kunji ERS, Driessen AJM, Suarez JE& Konings WN (1996) Bactericidal mode of action of plantaricin C. Appl. Environ. Microbiol. 62: 2701–2709.

    Google Scholar 

  • Guder A, Wiedemann I& Sahl H-G (2000) Post-translationally modified bacteriocins-the lantibiotics. Biopolymers 55: 62–73.

    Google Scholar 

  • Haas W, Shephard BD& Gilmore MS (2002) Two-component regulator of Enterococcus faecalis cytolysin responds to quorum sensing auto-induction. Nature 415: 84–87.

    Google Scholar 

  • Harris LJ, Fleming HP& Klaenhammer TR (1991) Sensitivity and resistance of Listeria monocytogenes ATCC 19115, Scott A and UAL500 to nisin. J. Food. Prot. 54: 836–840.

    Google Scholar 

  • Håvarstein LS, Diep DB& Nes IF (1995) A family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export. Mol. Microbiol. 16: 229–240.

    Google Scholar 

  • Holo H, Jeknic Z, Daeschel M, Stevanovic S& Nes I (2001) Plantaricin W from Lactobacillus plantarum belongs to a new family of two-component lantibiotics. Microbiology 147: 643–651.

    Google Scholar 

  • Huot E, Meghrous J, Barrena-Gonzalez C& Petitdemange H (1996) Bacteriocin J46, a new bacteriocin produced by Lactococcus lactis subsp. cremoris J46: isolation and characterization of the protein and its gene. Anaerobe 2: 137–145.

    Google Scholar 

  • Hynes WL, Friend VL& Ferretti JJ (1994) Duplication of the lantibiotic structural gene in M-type 49 group A streptococcus strains producing streptococcin A-M49. Appl. Environ. Microbiol. 60: 4207–4209.

    Google Scholar 

  • Ike Y, Hashimoto H& Clewell DB (1987) High incidence of hemolysin production by Enterococcus (Streptococcus) faecalis strains associated with human parenteral infections. J Clin. Microbiol. 25: 1524–1528

    Google Scholar 

  • Ike Y, Clewell DB, Segarra RA& Gilmore MS (1990) Genetic analysis of the pAD1 hemolysin/bacteriocin determinant in Enterococcus faecalis: Tn917 insertional mutagenesis and cloning. J. Bacteriol. 172: 155–163.

    Google Scholar 

  • Jack RW, Benz R, Tagg JR& Sahl H-G (1994) The mode of action of SA-FF22, a lantibiotic from Streptococcus pyogenes strain FF22. Eur. J. Biochem. 219: 699–705.

    Google Scholar 

  • Jack RW, Bierbaum G.& Sahl H-G (1998) Lantibiotics and Related Peptides. Springer, New York.

    Google Scholar 

  • Jarvis B, Farr J. Partial purification, specificity and mechanism of action of the nisin-inactivating enzyme from Bacillus cereus. Biochim. Biophys. Acta. 1971. 227: 232–240.

    Google Scholar 

  • Jett DD, Jenson HG, Nordquist RE& Gilmore MS. (1992) Contribution of the pAD1-encoded cytolysin to the severity of experimental Enterococcus faecalis endophthalmilis. Infect. Immun. 60: 2445–2452.

    Google Scholar 

  • Kalmokoff ML& Teather RM (1999). Isolation and characterisation of a bacteriocin, Butyrivibriocin AR10, from the ruminal anaerobe Butyrivibrio fibrisolvens AR10: evidence in support of the widespread occurrence of bacteriocin-like activity among ruminal isolates of B. fibrisolvens. Appl. Environ. Microbiol. 63: 394–402.

    Google Scholar 

  • Kellner R, Jung G& Sahl H-G (1991) Structure elucidation of the tricyclic lantibiotic Pep5 containing eight positively charged amino acids. In: Sahl H-G& Jung J (Eds) Nisin and Novel (pp 141–158). ESCOM Scientific Publishers BV, Leiden.

    Google Scholar 

  • Kimura H, Matsusaki H, Sashihara T, Sonomoto K& Ishizaki A (1998) Purification and partial identifiaction of bacteriocin ISK-1, a new lantibiotic produced by Pediococcus sp. ISK-1. Biosci. Biotechnol. Biochem. 62: 2341–2345.

    Google Scholar 

  • Klein C& Entian K-D (1994) Genes involved in self-protection against the lantibiotic subtilin produced by Bacillus subtilis ATCC6633. Appl. Environ. Microbiol. 60: 2793–2801.

    Google Scholar 

  • Klein C, Kaletta C& Entian K-D (1993) Biosynthesis of the lantibiotic subtilin is regulated by a histidine kinase/response regulator system. Appl. Environ. Microbiol. 59: 296–303.

    Google Scholar 

  • Krull RE, Chen P, Novak J, Kirk M, Barnes S, Baker J, Krishna NR& Caufield PW. (2000) Biochemical structural analysis of the lantibiotic mutacin II. J. Biol. Chem. 26: 15845–15850.

    Google Scholar 

  • Kuipers OP, Beerthuyzen MM, Siezen RJ& de Vos WM (1993) Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis: requirement of expression of the nisA and nisI genes for development of immunity. Eur. J. Biochem. 216: 281–291.

    Google Scholar 

  • Kuipers OP, Rollema HS, Yap G. J, Boot H, Siezen RJ& de Vos WM (1992) Engineering dehydrated amino acid residues in the antimicrobial peptide nisin. J. Biol. Chem. 267: 24340–24346.

    Google Scholar 

  • Kuipers OP, Beerthuyzen MM, De Ruyter PG, Luesink EJ,& De Vos WM (1995) Autoregulation of nisin biosynthesis in Lactococcus lactis by signal transduction. J. Biol. Chem. 270: 27299–27304.

    Google Scholar 

  • Lavanant H, Derrick PJ, Heck AJ& Mellon FA (1998) Analysis of nisin A and some of its variants using Fourier transform ion cyclotron resonance mass spectrometry Anal. Biochem. 255: 74–89.

    Google Scholar 

  • Lian L-Y, Chan WC, Morlaey SD, Roberts GCK, Bycroft, BW & Jackson D (1991) Solution structures of nisin and its two major degradation products determined by NMR. Biochem. J. 283: 413–420.

    Google Scholar 

  • Linnet PE& Strominger JL (1973) Additional antibiotic inhibitors of peptidoglycan biosynthesis. Antimicrobiol. Agents Chemother. 4: 231–236.

    Google Scholar 

  • McAuliffe O, Hill C, Ross RP (1999) Inhibition of Listeria monocytogenes in cottage cheese manufactured with a lacticin 3147-producing starter culture. J. Appl. Microbiol. 86: 251–256.

    Google Scholar 

  • McAuliffe O, Ryan MP, Ross RP, Hill C, Breeuwer P& Abee T (1998) Lacticin 3147, a broad-spectrum bacteriocin which selectively dissipates the membrane potential. Appl. Environ. Microbiol. 64: 439–445.

    Google Scholar 

  • McAuliffe, O, Hill C& Ross R P (2000) Identification and overexpression of ltnI, a novel gene which confers immunity to the two-component lantibiotic, lacticin 3147. Microbiology 146: 129–138.

    Google Scholar 

  • McAuliffe O, O'Keeffe T, Hill C& Ross RP (2001a) Regulation of immunity to the two-component lantibiotic, lacticin 3147, by the transcriptional repressor LtnR. Mol. Microbiol. 39: 982–993.

    Google Scholar 

  • McAuliffe O, Ross RP& Hill C (2001b) Lantibiotics: structure, biosynthesis and mode of action. FEMS Microbiol. Rev. 25: 285–308.

    Google Scholar 

  • Meyer C, Bierbaum G, Heidrich C, Reis M, Suling J, Iglesias-Wind MI, Kempter C, Molitor E& Sahl HG. Nucleotide sequence of the lantibiotic Pep5 biosynthetic gene cluster and functional analysis of PepP and PepC. Evidence for a role of PepC in thioether formation. Eur. J. Biochem. 1995. 232: 478–489.

    Google Scholar 

  • Mortvedt C I, Nissen-Meyer J, Sletten K,& Nes IF (1991) Purification and amino acid sequence of lactocin S, a bacteriocin produced by Lactobacillus sake L45. Appl. Environ. Microbiol. 57: 1829–1834.

    Google Scholar 

  • Mortvedt-Abilgaard CI, Nissen-Meyer J, Jelle B, Grenov B, Skaugen M& Nes IF (1995) Production and pH-dependent bacericidal activity of lactocin S, a lantibiotic from Lactobacillus sake L45. Appl. Environ. Microbiol. 61: 175–179.

    Google Scholar 

  • Navaratna, MADB, Sahl H-G& Tagg JR (1998) Two-component anti-Staphylococcus aureus lantibiotic activity produced by Staphylococcus aureus C55. Appl. Environ. Microbiol. 64: 4803–4808.

    Google Scholar 

  • Navaratna MA, Sahl H-G& Tagg JR (1999) Identification of genes encoding two-component lantibiotic production in Staphylococcus aureus strain C55 and other phage group II S. aureus strains and demonstration of an association with the exfoliative toxin B gene. Infect. Immun. 67: 4268–4271.

    Google Scholar 

  • Neis S, Bierbaum G, Josten C, Pag MU, Kempter C, Jung G& Sahl H-G (1997) Effect of leader peptide mutations on biosynthesis of the lantibiotic Pep5. FEMS Microbiol. Lett. 149: 249–255.

    Google Scholar 

  • Nes I F, Diep DB, Håvarstein LS, Brurberg MB, Eijsink V& Holo H (1996) Biosynthesis of bacteriocins in lactic acid bacteria. Antonie van Leeuwenhoek 70: 113–128.

    Google Scholar 

  • Otto M, Peschel A& Götz F (1998) Producer self-protection against the lantibiotic epidermin by the ABC transporter EpiFEG of Staphylococcus epidermidis Tu3298. FEMS Microbiol. Lett. 166: 203–211.

    Google Scholar 

  • Peschel A& Gotz F. Analysis of the Staphylococcus epidermidis genes epiF,-E, and-G involved in epidermin immunity. J. Bacteriol. 1996. 178: 531–536.

    Google Scholar 

  • Peschel A, Schnell N, Hille M, Entian K-D& Götz F (1997) Secretion of the lantibiotics epidermin and gallidermin: sequence analysis of the genes gdmT and gdmH, their influence on epidermin production and their regulation by EpiQ. Mol. Gen. Genet. 254: 312–318.

    Google Scholar 

  • Piard, J-C, Muriana PM, Desmazeaud MJ& Klaenhammer TR (1992) Purification and partial characterisation of lacticin 481, a lanthionine-containing bacteriocin produced by Lactococcus lactis subsp. lactis CNRZ481. Appl. Environ. Microbiol. 58: 279–284.

    Google Scholar 

  • Piard J-C, Kuipers OP, Rollema H S, Desmazeuad M J& de Vos WM (1993) Structure, organization and expression of the lct gene for lacticin 481, a novel lantibiotic produced by Lactococcus lactis. J. Biol. Chem. 268: 16361–16368.

    Google Scholar 

  • Prasch T, Naumann T, Markert RL, Sattler M, Schubert W, Schaal S, Bauch M, Kogler H& Griesinger C. Constitution and solution conformation of the antibiotic mersacidin determined by NMR and molecular dynamics. Eur. J. Biochem. 1997. 224: 501–512.

    Google Scholar 

  • Pridmore D, Rekhif N, Pittett A-C, Suri B,& Mollet B (1996) Variacin, a new lanthionine-containing bacteriocin produced by Micrococcus varians: comparison to lacticin 481 of Lactococcus lactis. Appl. Environ. Microbiol. 62: 1799–1802.

    Google Scholar 

  • Qi F, Chen P& Caufield PW (1999) Functional analyses of the promoters in the lantibiotic mutacin II biosynthetic locus in Streptococcus mutans. Appl. Environ. Microbiol. 65: 652–658.

    Google Scholar 

  • Qiao M& Saris PE J (1996) Evidence for a role of NisT in transport of the lantibiotic nisin produced by Lactococcus lactis N8. FEMS Microbiol. Lett. 144: 89–93.

    Google Scholar 

  • Qiao M, Immonen T, Koponen O& Saris PE J (1995) The cellular location and effect on nisin imunity of the NisI protein from Lactococcus lactis N8 expressed in Escherichia coli and L. lactis. FEMS Microbiol. Lett. 131: 75–80.

    Google Scholar 

  • Rogers LA& Whittier EO (1928) Limiting factors in lactic fermentation. J. Bacteriol. 16: 211–14.

    Google Scholar 

  • Reisinger P, Seidel H, Tschesche H,& Hammes WP (1980) The effect of nisin on murein synthesis. Arch. Microbiol. 127: 187–193.

    Google Scholar 

  • Reminger A, Eijsink VGH, Ehrmann MA, Sletten K, Nes IF& Vogel RF (1999) Purification and partial amino acid sequence of plantaricin 1.25a and 1.25b, two bacteriocins produced by Lactobacillus plantarum TMW1.25. J. Appl. Microbiol. 86: 1053–1058.

    Google Scholar 

  • Rince A, Dufour A, Le Pogam S, Thuault D, Bourgeois C M& Le Pennec JP (1994) Cloning, expression and nucleotide sequence of genes involved in production of lactococcin DR, a bacteriocin from Lactococcus lactis subsp. lactis. Appl. Environ. Microbiol. 60: 652–1657.

    Google Scholar 

  • Rince A, Dufour A, Uguen P, Le Pennec J-P& Haras D (1997) Characterization of the lacticin 481 operon: the Lactococcus lactis genes lctF, lctE, and lctG encode a putative ABC transporter involved in bacteriocin immunity. Appl. Environ. Microbiol. 63: 4252–4260.

    Google Scholar 

  • Rodríguez JM, Cintas LM, Casaus P, Suárez A& Hernández PE (1995) PCR detection of the lactocin S structural gene in bacteriocin-producing lactobacilli from meat. Appl. Environ. Microbiol. 61: 2802–2805.

    Google Scholar 

  • Rogers LA& Whittier ED (1928) Limiting factors in lactic fermentation. J. Bacteriol. 16: 211–229.

    Google Scholar 

  • Ross KF, Ronson CW& Tagg JR (1993) Isolation and characterisation of the lantibiotic salivaricin A and its structural gene salA from Streptococcus salivarius 20P3. Appl Environ. Microbiol. 59: 2014–2021.

    Google Scholar 

  • Ross RP, Galvin M, McAuliffe O, Morgan SM, Ryan MP, Twomey DP, Meaney WJ& Hill C (1999) Developing applications for lactococcal bacteriocins. Antonie van Leeuwenhoek 76: 337–346.

    Google Scholar 

  • Ruhr E& Sahl H-G (1985) Mode of action of the peptide antibiotic nisin and influence on the membrane potential of whole cells and on artificial membrane vesicles. Antimicrobiol. Agents Chemother. 27: 841–845.

    Google Scholar 

  • Ryan MP, Rea MC, Hill C& Ross RP (1996) An application in Cheddar cheese manufacture for a strain of Lactococcus lactis producing a novel broad spectrum bacteriocin, lacticin 3147. Appl. Environ. Microbiol. 62: 612–619.

    Google Scholar 

  • Ryan MP, Meaney WJ, Ross RP& Hill C (1998) Evaluation of lacticin 3147 and a teat seal containing bacteriocin for the inhibition of mastitis pathogens. Appl. Environ. Microbiol. 64: 2287–2290.

    Google Scholar 

  • Ryan MP, Jack R, Josten W, Sahl H-G, Jung G, Ross, RP& Hill C (1999) Extensive-translational modification, including a serine to D-alanine conversion, in the two-component lantibiotic, lacticin 3147. J. Biol. Chem. 274: 37544–37550.

    Google Scholar 

  • Sahl H-G, Kordel M& Benz R (1987) Voltage-dependent depolarization of bacterial membranes and artificial lipid bilayers by the peptide antibiotic nisin. Arch. Microbiol. 149: 120–124.

    Google Scholar 

  • Sahl H-G& Bierbaum G (1998) Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from grampositive bacteria. Annu. Rev. Microbiol. 52: 41–79.

    Google Scholar 

  • Segarra RA, Booth MC, Morales DA, Huycke MM& Gilmore MS (1991) Molecular characterization of the Enterococcus faecalis cytolysin activator. Infect. Immun. 59: 1239–1246.

    Google Scholar 

  • Siegers K& Entian K-D (1995) Genes involved in immunity to the lantibiotic nisin produced by Lactococcus lactis 6F3. Appl. Environ. Microbiol. 61: 1082–1089.

    Google Scholar 

  • Siezen RJ, Kuipers OP& de Vos WM (1996) Comparison of lantibiotic gene clusters and encoded proteins. Antonie van Leeuwenhoek 69: 171–184.

    Google Scholar 

  • Skaugen M, Nissen-Meyer J, Jung G, Stevanovic S, Sletten K, Abildgaard CIM& Nes I F (1994) In vivo conversion of L-serine to D-alanine in a ribosomally synthesized polypeptide. J. Biol. Chem. 269: 27183–27185.

    Google Scholar 

  • Skaugen M, Abildgaard CIM& Nes I F (1997) Organisation and expression of a gene cluster involved in the biosynthesis of the lantibiotic, lactocin S. Mol. Gen. Genet. 253: 674–686.

    Google Scholar 

  • Skaugen M, Anderson EL, Christie VH&Nes I (2002) Identification, characterisation and expression of a second bicistronic operon involved in the production of lactocin S in Lactocbacillus sake L45. Appl. Environ. Microbiol. (in press).

  • Takami H, Nakasone K, Takaki Y, Maeno G, Sasaki R, Masui N, Fuji F, Hirama C, Nakamura Y, Ogasawara N, Kuhara S& Horikoshi K (2000) Complete genome sequence of the alkaliphilic bacterium Bacillus halodurans and genomic sequence comparison with Bacillus subtilis. Nucleic Acids Res. 28: 4317–4331.

    Google Scholar 

  • Turner DL, Brennan L, Meyer HE, Lohaus C, Siethoff C, Costa HS, Gonzalez B, Santos H& Suárez JE (1999) Solution structure of plantaricin C, a novel lantibiotic. Eur. J. Biochem. 264: 833–839.

    Google Scholar 

  • Twomey DP, Wheelock AI, Flynn J, Meaney WJ, Hill C& Ross RP (2000) Protection against Staphylococcus aureus mastitis in dairy cows using a bismuth-based teat seal containing the bacteriocin, lacticin 3147. J. Dairy Sci. 83: 1981–1988.

    Google Scholar 

  • Uguen P, Hamelin J, le Pennec J-P& Blanco C (1999) Influence of osmolarity and the presence of an osmoprotectant on Lactococcus lactis growth and bacteriocin production. Appl. Environ. Microbiol. 65: 291–293.

    Google Scholar 

  • van de Ven FJM, van den Hooven HW, Konings RNH& Hilbers CW (1991) NMR-studies of lantibiotics: the structure of nisin in aqueous solution. Eur. J. Biochem. 202: 1181–1188.

    Google Scholar 

  • van den Hooven HW, Doeland CC, van den Kamp M, Konings RN, Hilbers CW& van den Ven FJ (1996a) Three-dimensional structure of the lantibiotic nisin in the presence of membrane mimetic micelles of dodecylphosphocholine and of sodium dodecysulphate. Eur. J. Biochem. 235: 382–393.

    Google Scholar 

  • van den Hooven HW, Lagerwerf FM, Heerma W, Haverkamp J, Piard JC, Hilbers CH, Siezen RJ, Kuipers OP& Rollema HS (1996b) The structure of the lantibiotic lacticin 481 produced by Lactococcus lactis: location of the thioether bridges. FEBS Lett. 391: 317–322.

    Google Scholar 

  • van den Hooven HW, Rollema HS, Siezen RJ, Hilbers CW& Kuipers OP (1997) Structural features of the final intermediate in the biosynthesis of the lantibiotic nisin. Influence of the leader peptide. Biochemistry 36: 14137–14145.

    Google Scholar 

  • van der Meer JR, Polman J, Beerthuyzen MM, Siezen RJ, Kuipers OP& de Vos WM (1993) Characterization of the Lactococcus lactis nisin A operon: genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis. J. Bacteriol. 175: 2578–2588.

    Google Scholar 

  • van der Meer JR, Rollema HS, Siezen RJ, Beerthuyzen MM, Kuipers OP& de Vos WM(1994) Influence of amino acid substitutions in the nisin leader peptide on biosynthesis and secretion of nisin by Lactococcus lactis. J. Biol. Chem. 269: 3555–3562.

    Google Scholar 

  • Walker JE, Saraste M, Runswick MJ& Gay NJ (1982) Distantly related sequences in the β-and β-subunits of ATP synthase, myosin, kinases and other ATP requiring enzymes and a common nucleotide binding fold. EMBO J. 1: 945–951.

    Google Scholar 

  • Whitehead HR (1933) A substance inhibiting bacterial growth, produced by certain strains of lactic streptococci. Biochem. J. 27: 1793–1800.

    Google Scholar 

  • Wiedemann I, Breukink E, van Kraaij C, Kuipers O, Bierbaum G, de Kruijff B& Sahl H-G (2001) Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and the inhibition of cell wall biosynthesis for potent antibiotic activity. J. Biol. Chem. 276: 1772–1779.

    Google Scholar 

  • Woodruff WA, Novak J& Caufield PW (1998) Sequence analysis of mutA and mutM genes involved in the biosynthesis of the lantibiotic mutacin II in Streptococcus mutans. Gene 206: 37–43.

    Google Scholar 

  • Yamaguchi T, Hayashi T, Takami H, Ohnishi M, Murata T, Nakayama K, Asakawa M, Ohara M, Komatsuzawa H& Sugai M (2001) Complete nucleotide sequence of a Staphylococcus aureus exfoliative toxin B plasmid and identification of a novel ADP-ribosyltransferase, EDIN-C. Infect. Immun. 69: 7760–7771.

    Google Scholar 

  • Zimmermann N& Jung G (1997) The three dimensional solution structure of the lantibiotic murein-biosynthesis-inhibitor actagardine determined by NMR. Eur. J. Biochem. 246: 809–819.

    Google Scholar 

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Correspondence to C. Hill.

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Twomey, D., Ross, R.P., Ryan, M. et al. Lantibiotics produced by lactic acid bacteria: structure, function and applications. Antonie Van Leeuwenhoek 82, 165–185 (2002). https://doi.org/10.1023/A:1020660321724

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