Skip to main content
Log in

Biosynthesis of bacteriocins in lactic acid bacteria

  • Genetics
  • Published:
Antonie van Leeuwenhoek Aims and scope Submit manuscript

Summary

A large number of new bacteriocins in lactic acid bacteria (LAB) has been characterized in recent years. Most of the new bacteriocins belong to the class II bacteriocins which are small (30–100 amino acids) heat-stable and commonly not post-translationally modified. While most bacteriocin producers synthesize only one bacteriocin, it has been shown that several LAB produce multiple bacteriocins (2–3 bacteriocins).

Based on common features, some of the class II bacteriocins can be divided into separate groups such as the pediocin-like and strong anti-listeria bacteriocins, the two-peptide bacteriocins, and bacteriocins with a sec-dependent signal sequence. With the exception of the very few bacteriocins containing a sec-dependent signal sequence, class II bacteriocins are synthesized in a preform containing an N-terminal double-glycine leader. The double-glycine leader-containing bacteriocins are processed concomitant with externalization by a dedicated ABC-transporter which has been shown to possess an N-terminal proteolytic domain. The production of some class II bacteriocins (plantaricins of Lactobacillus plantarum C11 and sakacin P of Lactobacillus sake) have been shown to be transcriptionally regulated through a signal transduction system which consists of three components: an induction factor (IF), histidine protein kinase (HK) and a response regulator (RR). An identical regulatory system is probably regulating the transcription of the sakacin A and carnobacteriocin B2 operons. The regulation of bacteriocin production is unique, since the IF is a bacteriocin-like peptide with a double-glycine leader processed and externalized most probably by the dedicated ABC-transporter associated with the bacteriocin. However, IF is not constituting the bacteriocin activity of the bacterium, IF is only activating the transcripion of the regulated class II bacteriocin gene(s).

The present review discusses recent findings concerning biosynthesis, genetics, and regulation of class II bacteriocins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abee T 1995. Pore-forming bacteriocins of Gram-positive bacteria and self-protection mechanisms of producer organisms. FEMS Microbiol. Lett. 129: 1–10

    Google Scholar 

  • Allison GE, C Fremaux and TR Klaenhammer 1994. Expansion of bacteriocin activity and host range upon complementation of two peptides encoded within the Lactacin F operon. J. Bacteriol. 176: 2235–2241

    Google Scholar 

  • Allison GE, RW Worobo, ME Stiles and TR Klaenhammer 1995. Heterologous expresion of the lactacin F peptides by Carnobacterium piscicola LV17. Appl. Environ. Microbiol. 61: 1371–1377

    Google Scholar 

  • Aymerich T, H Holo, LS Håvarstein, M Hugas, M Garriga, IF Nes 1996. Biochemical and genetic characterization of enterocin A from Enterococcus faecium, a new antilisterial bacteriocin in the pediocin family of bacteriocins. Appl. Environ. Microbiol. 62: 1676–1682

    Google Scholar 

  • Axelsson L, A Holck, SE Birkeland, T Aukrust and H Blom 1993. Cloning and nucleotide sequencing of a gene from Lactobacillus sake LB706 necessary for sakacin A production and immunity. Appl. Environ. Microbiol. 59: 2868–2875

    Google Scholar 

  • Axelsson L and A Holck 1995. The genes involved in production of and immunity to sakacin A, a bacteriocin from Lactobacillus sake Lb706. J. Bacteriol. 177: 2125–2137

    Google Scholar 

  • Balaban N and RP Novick 1995. Autocrine regulation of toxin synthesis by Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 92: 1619–1623

    Google Scholar 

  • Bourret RB, KA Borkovich and MI Simon 1991. Signal transduction pathways involving protein phosphorylation in prokaryotes. An. Rev. Biochem. 60: 401–441

    Google Scholar 

  • Brurberg MB, IF Nes and V Eijsink 1996. Unpublished results

  • Chikindas MJ, MJ Garcia Garcera, AMDriessen, AM Lederboer, J Nissen-Meyer, IF Nes, T Abee, WN Konings and G Venema 1993. Pediocin PA-1, a bacteriocin from Pediococcus acidilactici PAC1.0, forms hydrophillic pores in the cytoplasmatic membrane of target cells. Appl. Environ. Microbiol. 59: 3577–3584

    Google Scholar 

  • Chikindas ML, K Venema, AM Ledeboer, G Venema and J Kok 1995. Expression of lactococcin A and pediocin PA-1 in heterologous hosts. Letters in Applied Microbiol. 21: 183–189

    Google Scholar 

  • De Vos WM, OP Kuipers, JRvan der Meer and RJ Siezen 1995. Maturation pathway of nisin and other lantibiotics: post-translationally modified antimicrobial peptides exported by gram-positive bacteria. Mol. Microbiol. 17: 427–337

    Google Scholar 

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

    Google Scholar 

  • Diep DB, LS Håvarstein and IF Nes 1995. A bacteriocin-like peptide induces bacteriocin synthesis in L. plantarum C11. Mol. Microbiol. 18: 631–639

    Google Scholar 

  • Diep DB, 1996. Characterization of the locus responsible for the bacteriocin production in Lactobacillus plantarum C11. J. Bacteriol. 178: 4472–4483

    Google Scholar 

  • Eisjink VGH, MB Brurberg, PH Middelhoven and IF Nes 1996. Induction of bacteriocin production in Lactobacillus sake by a secreted peptide. J. Bacteriol. 178: 2232–2237

    Google Scholar 

  • Engelke G, Z Gutowski-Eckel, P Kiesau, K Siegers, M Hammelmann and KD Entien 1994. Regulation of nisin biosynthesis and immunity of Lactococcus lactic 6F3. Appl. Environ. Microbiol. 60: 814–825

    Google Scholar 

  • Fath MJ, LH Zhang, J Rush and R Kolter 1994. Purification and characterization of colicin V from Eschericia coli culture supernatants. Biochemistry 33: 6911–6917

    Google Scholar 

  • Fimland G, OR Blingso, K Sletten, G Jung, IF Nes, J Nissen-Meyer 1996. New biological activity hybrid bacteriocins constructed by combining regions from various pediocin-like bacteriocins. Appl. Environ. Microbiol. 62: 000–000

    Google Scholar 

  • Franke CM, KJ Leenhout, AJ Haandrikman, J Kok, G Venema and K Venema 1996. Topology of LcnD, a protein implicated in the transport of bacteriocins from Lactococcus lactic. J. Bacteriol. 176: 1766–1769

    Google Scholar 

  • Fremaux C, C Ahn and TR Klaenhammer 1993. Molecular analysis of the lactocin F operon. Appl. Environ. Microbiol. 59: 3906–3915

    Google Scholar 

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

    Google Scholar 

  • Gilson L, HK Mahanty, R Kolter (1990). Genetic analysis of an MDR-like export system: the secretion of colicin V. EMBO J. 9: 3875–3884

    Google Scholar 

  • Guangyong J, RC Blavis and RP Novick (1995). Cell density of staphylococcal virulence mediated by an octapeptide pheromone. Proc. Natl. Acad. Sci. USA 92: 12055–12059

    Google Scholar 

  • Hastings JW, M Sailer, K Johnson, KL Roy, JC Vederas and ME Stiles 1991. Characterization of leucocin A-UAL 187 and cloning of the bacteriocin gene from Leuconostoc gelidum. J. Bacteriol. 173: 7491–7500

    Google Scholar 

  • Hechard Y, DB Derijard, F Letellier and Y Cenatiempo 1992. Characterization and purification of mesentericin Y105, an anti-Listeria bacteriocin from Leuconostoc mesenteroides. J. Gen. Microbiol. 138: 2725–2731

    Google Scholar 

  • Henderson JT, AL Chopko and PDvan Wasserman 1992. Purification and primary structure of pediocin PA-1 produced by Pediococcus acidilactici PAC1.0. Arch. Biochem. Biophys. 295: 5–12

    Google Scholar 

  • Hoch JA and TJ Silhavy (Eds.), 1995. Two-Component Signal Transduction. ASM Press, Washington, D.C. USA

    Google Scholar 

  • Holck A, L Axelsson, SE Birkeland, T Aukrust and H Blom 1992. Purification and amino acid sequence of sakacin A, a bacteriocin from Lactobacillus sake Lb 706. J. Gen. Microbiol. 138: 2715–2720

    Google Scholar 

  • Holo H. (1996) Resistance and immunity to bacteriocins of lactic acid bacteria. Manuscript submitted to Can. J. Microbiol.

  • Holo H, Ø Nilssen and IF Nes 1991. Lactococcin A, a new bacteriocin from Lactococcus lactis subsp. cremoris: isolation and characterization of the protein and its gene. J. Bacteriol. 173: 3879–3887

    Google Scholar 

  • Huehne K, A Holck, L Axelson and L Kroeckel 1996. Analysis of sakacin P gene cluster from Lactobacillus sake LB674 and its expression in sakacin P negative L. sake strains. Microbiology. 142: 1437–1448

    Google Scholar 

  • Håvarstein LS, H Holo and IF Nes 1994. The leader peptide of colicin V shares consensus sequences with leader peptides that are common amongst peptide bacteriocins produced by Grampositive bacteria. Microbiol. 140: 2383–2389

    Google Scholar 

  • Håvarstein LS, G Coomaraswamy and DA Morrison 1995. An unidentified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. Proc. Natl. Acad. Sci. USA 92: 11140–11144

    Google Scholar 

  • Håvarstein LS, BD Diep and IF Nes 1995. A Family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export. Mol. Microbiol. 16: 229–240

    Google Scholar 

  • Jack RW, JR Tagg and B Ray (1995). Bacteriocins of Gram-Positive Bacteria. Microbiol. Rev. 59: 171–200

    Google Scholar 

  • Jiménez-Diaz R, JL Ruiz-Barba, DP Cathcart, H Holo, IF Nes, KH Sletten and PJ Warner 1995. Purification and partial amino acid sequence of plantaricin S, a bacteriocin produced by Lactobacillus plantarum LPCO10, the activity of which depends on the complementary action of two peptides. Appl. Environ. Microbiol. 61: 4459–4463

    Google Scholar 

  • Jiménez-Diaz R, RM Rios-Sánchez, M Desmazeaud, JL Ruiz-Barba and JC Piard 1993. PlantaricinS and T, two new bactriocins produced by Lactobacillus plantarum LPCO10 isolated from a green olive fermentation. Appl. Environ. Microbiol. 59: 1416–1424

    Google Scholar 

  • Kanatani K, M Oshimura and K Sano 1995. Isolation and charcterization of acidocin A and cloning of the bacteriocin gene from Lactobacillus acidophilus. Appl. Environ. Microbiol. 61: 1061–1067

    Google Scholar 

  • Karlson P & M. Lüscher 1959. Pheromones a new term of class of biologically active substances? 183: 55–56

    Google Scholar 

  • Klaenhammer TR 1993. Genetics of bacteriocins produced by lactic acid bacteria. FEMS Microbiol. Rev. 12: 39–86

    Google Scholar 

  • Kuipers OP, HS Rollema, WMG Yap, HJ Boot, RJ Siezen and WM deVos 1992. Engineering dehydrated amino acid residues in the antimicrobial peptide nisin. J. Biol. Chem. 267: 24340–24346

    Google Scholar 

  • Kuipers OP, MM Beerthuyzen, PGGA deRuyter, EJ Luesink and WM deVos 1995. Autoregulation of nisin biosynthesis in Lactococcus lactic by signal transduction. J. Biol. Chem. 270: 281–291

    Google Scholar 

  • Konings RNH and CW Hilbers (Eds.), 1996. Lantibiotics: A Unique Group of Antibiotic Peptides. Antonie van Leeuwenhoek Int. J. Gen. Molec. Microbiol. 69: Issue 2

  • Larsen AG and B Nørrung 1993. Inhibition of Listeria monocytogenes by bavaricin A, a bacteriocin produced by Lactobacillus bavaricus MI401. Lett. Appl. Microbiol. 17: 132–134

    Google Scholar 

  • Leer RL, JMBM van der Vossen, Mvan Giezen, JMvan Noort and PH Pouwels (1995): Genetic analysis of acidocin B, a novel bacteriocin produced by Lactobacillus acidophilus. Microbiol. 141: 1629–1635

    Google Scholar 

  • Magnusson R, J Solomon and AD Grossman 1994. Biochemical and genetic characterization of a competence pheromone from B. subtilis. Cell 77: 207–216

    Google Scholar 

  • Marugg JD, CF Gonzales, BS Kunka, AM Ledeboer, MJ Pucci, MY Toonen, SA Walker, LCM Zoetmulder and PA Vandenbergh 1992. Cloning, expression, and nucleotide sequence of genes involved in production of pediocin PA-1, a bacteriocin from Pediococcus acidilactici PAC1.0. Appl. Environ. Microbiol. 58: 2360–2367

    Google Scholar 

  • Morfeldt E, L Janzon, S Arvidson and S Löfdalh 1988. Cloning of a chromosomal locus (exp) which regulates the expression of several exoprotein genes in Staphylococcus aureus. Mol. Gen. Genet. 211: 435–440

    Google Scholar 

  • Motlagh AM, AK Buhunia, F Szostek, TR Hansen, MC Johnson, B Ray 1992. Nucleotide and amino acid sequence of pap gene pediocin AcH) produced in Pediococcus acididlactici H. Lett. Appl. Microbiol. 15: 45–48

    Google Scholar 

  • Muriana PM and TR Klaenhammer 1991. Cloning, phenotypic expression, and DNA sequence of the gene for lactacin F, an antimicrobial peptide produced by Lactobacillus spp. J. Bacteriol. 173: 1779–1788

    Google Scholar 

  • Nes IF, LS Håvarstein and H Holo 1995. Genetic of non-lantibiotics bacteriocins. In Genetics of Streptococci, Enterococci and Lactococci. (J. J. Ferretti, M. S. Gilmore, T. R. Klaenhammer, and F. Brown, Eds.). Karger, New York, pp. 645–651

    Google Scholar 

  • Nieto Lozano JC, J Nissen-Meyer, K Sletten, C Peláz and IF Nes 1992. Purification and amino acid sequence of a bacteriocin produced by Pediococcus acidilactici. J. Gen. Microbiol. 138: 1985–1990

    Google Scholar 

  • Nissen-Meyer J, H Holo, LS Håvarstein, K Sletten and IF Nes 1992. A novel lactococcal bacteriocin whose activity depends on the complementary action of two peptides. J. Bacteriol. 174: 5686–5692

    Google Scholar 

  • Nissen-Meyer J, LS Håvarstein, H Holo, K Sletten and IF Nes 1993a. Association of the lactococcin A immunity factor with the cell membrane: purification and characterization of the immunity factor. J. Gen. Microbiol. 139: 1503–1509

    Google Scholar 

  • Nissen-Meyer J, AG Larsen, K Sletten, M Daeschel and IF Nes 1993b. Purifiaction and characterization of plantaricin A, a Lactobacillus plantarum bacteriocin whose activity depends on the action of two peptides. J. Gen. Microbiol. 139: 1973–1978

    Google Scholar 

  • O'Brian GJ and HK Mahanty 1996. Complete nucleotide sequence of microcin 24 genetic region and analysis of a new ABC transporter. Accession number ECU47048

  • Parkinson JS and EC Kofoid 1992. Communication modules in bacterial signaling proteins. Annu. Rev. Genet. 26: 71–112

    Google Scholar 

  • Pestova EV, LS Håvarstein and DA Morrison 1996. Regulation of transformability by an auto-induced peptide pheromone and a two-component regulatory system. Molec. Microbiol. 21: 855–864

    Google Scholar 

  • Piard JC, OP Kuipers, HS Rolema, MJ Deamzeaud and WM de Vos 1993. Structure, organization and expression of the lct gene for lacticin 481, a novel lantibiotic produced by Lactococcus lactic. J. Biol. Chem. 268: 16361–16368

    Google Scholar 

  • Quadri LEN, KL Roy, JC Vederas and ME Stiles 1995a. Characterization of four genes involved in the production of antimicrobial peptides by Carnobacterium piscicola LV17B. Published DNA sequence with accession nr. 147121. em-bl.new

  • Quadri LEN, M Sailer, MR Terebiznik, KL Roy, JC Vederas and ME Stiles 1995b. Characterization of the protein conferring immunity to the antimicrobial peptide carnobacteriocin B2 and expression of the carnobacteriocins B2 and BM1. J. Bacteriol. 177: 1144–1151

    Google Scholar 

  • Quadri LEN, M Sailers, KL Roy, JC Vederas and ME Stiles 1994. Chemical and genetic characterization of bacteriocins produced by Carnobacterium piscicola LV17B. J. Biol. Chem. 269: 12204–12211

    Google Scholar 

  • Ray B 1992. Pediocin(s) of Pediococcus acidilactici as a Food Biopreservative. Page 265–322. In: Food Biopreservatives of Microbial Origin. Eds. B. Ray and M. Daeschel. CRC Press Inc. Bocan Raton, Forida

    Google Scholar 

  • Ross KF, CW Ronson and JR Tagg 1993. Isolation and characterization of the lantibiotic salavaricin A and its structural gene salA from Streptococcus salivarius 20P3. Appl. Environ. Microbiol. 60: 1652–1657

    Google Scholar 

  • Sahl HG, RW Jack and G Bierbaum (1995): Biosynthesis and biological activities of lantibiotics with unique post-translational modifications. Eur. J. Biochem. 230: 827–853

    Google Scholar 

  • Saucier L, A Poon and ME Stiles (1995). Induction of bacteriocin in Carnobacterium piscicola LV 17. J. Appl. Bacteriol. 78: 684–690

    Google Scholar 

  • Stock JB, AJ Ninfa and AM Stock 1989. Protein phosphorylation and regulation of adaptive responses in bacteria. Microbiol. Rev. 53: 450–490

    Google Scholar 

  • Stoddard GW, JP Petzel, MJ Van Belkum, J Kok and LL McKay 1992. Molecular analyses of the lactococcin A gene cluster from Lactococcus lactis subsp. lactis biovar diacetylactis WM4. Appl. Environ. Microbiol. 58: 1952–1961

    Google Scholar 

  • Tichaczek PS, J Nissen-Meyer, IF Nes, RF Vogel and WP Hammes 1992. Characterization of the bacteriocins curvacin A from Lactobacillus curvatus LTH1174 and sakacin from L. sake LTH673. Syst. Appl. Microbiol. 15: 460–468

    Google Scholar 

  • , RF Vogel and WP Hammes 1993. Cloning and sequencing of curA encoding curvacin A, the bacteriocin produced by Lactobacillus curvatus LTH1174. Arch. Microbiol. 160: 279–283

    Google Scholar 

  • Tichaczek PS 1994. Cloning and sequencing of sakP encoding sakacin P, the bacteriocin produced by Lactobacillus sake LTH 673. Microbiology 140: 361–367

    Google Scholar 

  • Van Belkum MJ, Hayema BJ, Leeninga RE, Kok J and G Venema (1991). Organization and nucleotide sequences of two lactococcal bacteriocin operons. Applied and Environmental Microbiology 57: 492–498

    Google Scholar 

  • Van Belkum MJ, J Kok and G Venema 1992. Cloning, sequencing, and expression in Escherichia coli of lcnB, a third bacteriocin determinant from the lactococcal bacteriocin plasmid p9B4-6. Appl. Environ. Microbiol. 58: 572–577

    Google Scholar 

  • Van Belkum MJ and ME Stiles (1995) Molecular characterization of genes involved in the production of the bacteriocin leucocin A from Leuconostoc gelidum. Appl. Environ. Microbiol. 61: 3573–3579

    Google Scholar 

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

    Google Scholar 

  • Venema K, T Abee, AJ Haandrikman, KJ Leenhouts, J Kok, WN Konings and GVenema 1993. Mode of action of lactococcin B, a thiol-activated bacteriocin from Lactococcus lactis. Appl. Environ. Microbiol. 59: 1041–1048

    Google Scholar 

  • Venema K, RE Haverkort, T Abee, AJ Haandrikman, KJ Leenhouts, LD Leij, G Venema and J Kok 1994. Mode of action of LciA, the lactococcin A immunity protein. Mol. Microbiol. 16: 521–532

    Google Scholar 

  • Venema K, J Kok, JD Marugg, MY Toonen, AM Ledeboer, G Venema and ML Chikindas 1995a. Functional analysis of the pediocin operon of Pediococcus acidilactici PAC1.0:PedB is the immunity protein and PedD is the precursor processing enzyme. Mol. Microbiol. 17: 515–522

    Google Scholar 

  • Venema K, MHA Dost, G Venema and J Kok 1996. Mutational analysis and chemical modification of lactococcin B, a bacteriocin produced by Lactococcus lactis. Manuscript

  • Venema K, MHA Dost, PAH Beun, AJ Haandrikman, G Venema and J Kok 1996. The genes for secretion of lactococins are located on the chromosom of Lactococcus lactis IL1403. Appl. Environ. Microbiol. 62: 1689–1692

    Google Scholar 

  • Worobo RW, T Henkel, M Sailer, KL Roy, JC Vederas and ME Stiles 1994. Characteristics and genetic determinant of a hydrophobic peptide bacteriocin, carnobacteriocin A, produced by Carnobacterium piscicola LV17A. Microbiology 140: 517–526

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nes, I.F., Diep, D.B., Håvarstein, L.S. et al. Biosynthesis of bacteriocins in lactic acid bacteria. Antonie van Leeuwenhoek 70, 113–128 (1996). https://doi.org/10.1007/BF00395929

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00395929

Keywords

Navigation