Skip to main content
SpringerLink
Log in

Class IIc or Circular Bacteriocins

  • Chapter
  • First Online:
Prokaryotic Antimicrobial Peptides

Abstract

The circular bacteriocins produced by Gram-positive bacteria represent a diverse class of antimicrobial peptides. These bacteriocins display enhanced stability compared to linear bacteriocins, which arises from their characteristic circular backbone. Currently, eight unique circular bacteriocins have been identified, and analysis of their gene clusters indicates that they likely utilize complex mechanisms for maturation and secretion, as well as for immunity. These bacteriocins target the cytoplasmic membrane of sensitive cells, leading to pore formation that results in loss of ions, dissipation of membrane potential, and ultimately, cell death. Structural studies suggest that despite variation in their sequences, most of these bacteriocins likely adopt a common three-dimensional architecture, consisting of four or five tightly packed helices encompassing a hydrophobic core. There are many mysteries surrounding the biosynthesis of these peptides, particularly in regard to the mechanism by which they are cyclized. Elucidation of such a mechanism may provide exciting new approaches to the bioengineering of new, stable, and antimicrobially active circular peptides.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abriouel H, Valdivia E, Gálvez A, Maqueda M (1998) Response of Salmonella choleraesuis LT2 spheroplasts and permeabilized cells to the bacteriocin AS-48. Appl Environ Microbiol 64:4623–4626

    CAS  Google Scholar 

  • Abriouel H, Valdivia E, Gálvez A, Maqueda M (2001) Influence of physico-chemical factors on the oligomerization and biological activity of bacteriocin AS-48. Curr Microbiol 42:89–95

    CAS  Google Scholar 

  • Ananou S, Gálvez A, Martínez-Bueno M, Maqueda M, Valdivia E (2005) Synergistic effect of enterocin AS-48 in combination with outer membrane permeabilizing treatments against Escherichia coli O157: H7. J Appl Microbiol 99:1364–1372

    Article  CAS  Google Scholar 

  • Arakawa K, Kawai Y, Ito Y, Nakamura K, Chujo T, Nishimura J, Kitazawa H, Saito T (2010) HPLC purification and re-evaluation of chemical identity of two circular bacteriocins, gassericin A and reutericin 6. Lett Appl Microbiol 50:406–411

    Article  CAS  Google Scholar 

  • Arakawa K, Kawai Y, Iioka H, Tanioka M, Nishimura J, Kitazawa H, Tsurumi K, Saito T (2009) Effects of gassericins A and T, bacteriocins produced by Lactobacillus gasseri, with glycine on custard cream preservation. J Dairy Sci 92:2365–2372

    Article  CAS  Google Scholar 

  • Babasaki K, Takao T, Shimonishi Y, Kurahashi K (1985) Subtilosin A, a new antibiotic peptide produced by Bacillus subtilis 168: isolation, structural analysis, and biogenesis. J Biochem 98:585–603

    CAS  Google Scholar 

  • Bayro MJ, Mukhopadhyay J, Swapna GVT, Huang JY, Ma LC, Sineva E, Dawson PE, Montelione GT, Ebright RH (2003) Structure of antibacterial peptide microcin J25: A 21-residue lariat protoknot. J Am Chem Soc 125:12382–12383

    Article  CAS  Google Scholar 

  • Blond A, Peduzzi J, Goulard C, Chiuchiolo MJ, Barthélémy M, Prigent Y, Salomón RA, Farías RN, Moreno F, Rebuffat S (1999) The cyclic structure of microcin J25, a 21-residue peptide antibiotic from Escherichia coli. Eur J Biochem 259:747–755

    Article  CAS  Google Scholar 

  • Blond A, Cheminant M, Ségalas-Milazzo I, Peduzzi J, Barthélémy M, Goulard C, Salomón R, Moreno F, Farías R, Rebuffat S (2001) Solution structure of microcin J25, the single macrocyclic antimicrobial peptide from Escherichia coli. Eur J Biochem 268:2124–2133

    Article  CAS  Google Scholar 

  • Chatterjee C, Paul M, Xie LL, van der Donk WA (2005) Biosynthesis and mode of action of lantibiotics. Chem Rev 105:633–683

    Article  CAS  Google Scholar 

  • Chen H, Hoover DG (2003) Bacteriocins and their food applications. Compr Rev Food Sci Food Saf 2:82–100

    CAS  Google Scholar 

  • Cotter PD, Hill C, Ross RP (2005) Bacteriocins: developing innate immunity for food. Nat Rev Microbiol 3:777–788

    Article  CAS  Google Scholar 

  • Craik DJ (2006) Chemistry – seamless proteins tie up their loose ends. Science 311:1563–1564

    Article  Google Scholar 

  • Craik DJ (2009) Circling the enemy: cyclic proteins in plant defence. Trends Plant Sci 14:328–335

    Article  CAS  Google Scholar 

  • Craik DJ, Daly NL, Saska I, Trabi M, Rosengren KJ (2003) Structures of naturally occurring circular proteins from bacteria. J Bacteriol 185:4011–4021

    Article  CAS  Google Scholar 

  • Daly NL, Rosengren KJ, Craik DJ (2009) Discovery, structure and biological activities of cyclotides. Adv Drug Deliv Rev 61:918–930

    Article  CAS  Google Scholar 

  • Diaz M, Valdivia E, Martínez-Bueno M, Fernández M, Soler-González AS, Ramírez-Rodrigo H, Maqueda M (2003) Characterization of a new operon, as-48EFGH, from the as-48 gene cluster involved in immunity to enterocin AS-48. Appl Environ Microbiol 69:1229–1236

    Article  CAS  Google Scholar 

  • Draper LA, Ross RP, Hill C, Cotter PD (2008) Lantibiotic immunity. Curr Protein Pept Sci 9:39–49

    Article  CAS  Google Scholar 

  • Drider D, Fimland G, Héchard Y, McMullen LM, Prévost H (2006) The continuing story of class IIa bacteriocins. Microbiol Mol Biol Rev 70:564–582

    Article  CAS  Google Scholar 

  • Franz CMAP, van Belkum MJ, Holzapfel WH, Abriouel H, Gálvez A (2007) Diversity of enterococcal bacteriocins and their grouping in a new classification scheme. FEMS Microbiol Rev 31:293–310

    Article  CAS  Google Scholar 

  • Gálvez A, Maqueda M, Martínez-Bueno M, Valdivia E (1989) Bactericidal and bacteriolytic action of peptide antibiotic AS-48 against gram-positive and gram-negative bacteria and other organisms. Res Microbiol 140:57–68

    Article  Google Scholar 

  • Gálvez A, Maqueda M, Martínez-Bueno M, Valdivia E (1991) Permeation of bacterical cells, permeation of cytoplasmic and artificial membrane vesicles, and channel formation on lipid bilayers by peptide antibiotic AS-48 J. Bacteriology 173:886–892

    Google Scholar 

  • Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server, p. 571-607. In: Walker JM (ed) The proteomics protocols handbook. Humana, NJ

    Google Scholar 

  • Gillon AD, Saska I, Jennings CV, Guarino RF, Craik DJ, Anderson MA (2008) Biosynthesis of circular proteins in plants. Plant J 53:505–515

    Article  CAS  Google Scholar 

  • Gondry M, Sauguet L, Belin P, Thai R, Amouroux R, Tellier C, Tuphile K, Jacquet M, Braud S, Courcon M, Masson C, Dubois S, Lautru S, Lecoq A, Hashimoto S, Genet R, Pernodet JL (2009) Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat Chem Biol 5:414–420

    Article  CAS  Google Scholar 

  • Gong XD, Martin-Visscher LA, Nahirney D, Vederas JC, Duszyk M (2009) The circular bacteriocin, carnocyclin A, forms anion-selective channels in lipid bilayers. Biochim Biophys Acta 1788:1797–1803

    Article  CAS  Google Scholar 

  • González C, Langdon GM, Bruix M, Gálvez A, Valdivia E, Maqueda M, Rico M (2000) Bacteriocin AS-48, a microbial cyclic polypeptide structurally and functionally related to mammalian NK-lysin. Proc Natl Acad Sci USA 97:11221–11226

    Article  Google Scholar 

  • HÃ¥varstein 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

    Article  Google Scholar 

  • Heng NCK, Tagg JR (2006) What’s in a name? Class distinction for bacteriocins. Nat Rev Microbiol 4:160

    Article  CAS  Google Scholar 

  • Huang T, Geng H, Miyyapuram VR, Sit CS, Vederas JC, Nakano MM (2009) Isolation of a variant of subtilosin A with hemolytic activity. J Bacteriol 191:5690–5696

    Article  CAS  Google Scholar 

  • Ireland DC, Colgravel ML, Nguyencong P, Daly NL, Craik DJ (2006) Discovery and characterization of a linear cyclotide from Viola odorata: Implications for the processing of circular proteins. J Mol Biol 357:1522–1535

    Article  CAS  Google Scholar 

  • Ito Y, Kawai Y, Arakawa K, Honme Y, Sasaki T, Saito T (2009) Conjugative plasmid from Lactobacillus gasseri LA39 that carries genes for production of and immunity to the circular bacteriocin gassericin A. Appl Environ Microbiol 75:6340–6351

    Article  CAS  Google Scholar 

  • Itoh T, Fujimoto Y, Kawai Y, Toba T, Saito T (1995) Inhibition of food-borne pathogenic bacteria by bacteriocins from Lactobacillus gasseri. Lett Appl Microbiol 21:137–141

    Article  CAS  Google Scholar 

  • Jiménez MA, Barrachi-Saccilotto AC, Valdivia E, Maqueda M, Rico M (2005) Design, NMR characterization and activity of a 21-residue peptide fragment of bacteriocin AS-48 containing its putative membrane interacting region. J Pept Sci 11:29–36

    Article  Google Scholar 

  • Kalmokoff ML, Cyr TD, Hefford MA, Whitford MF, Teather RM (2003) Butyrivibriocin AR10, a new cyclic bacteriocin produced by the ruminal anaerobe Butyrivibrio fibrisolvens AR10: characterization of the gene and peptide. Can J Microbiol 49:763–773

    Article  CAS  Google Scholar 

  • Kawai Y, Saito T, Kitazawa H, Itoh T (1998a) Gassericin A; an uncommon cyclic bacteriocin produced by Lactobacillus gasseri LA39 linked at N- and C-terminal ends. Biosci Biotechnol Biochem 62:2438–2440

    Article  CAS  Google Scholar 

  • Kawai Y, Saito T, Suzuki M, Itoh T (1998b) Sequence analysis by cloning of the structural gene of gassericin A, a hydrophobic bacteriocin produced by Lactobacillus gasseri LA39. Biosci Biotechnol Biochem 62:887–892

    Article  CAS  Google Scholar 

  • Kawai Y, Arakawa K, Itoh A, Saitoh B, Ishii Y, Nishimura J, Kitazawa H, Itoh T, Saito T (2003) Heterologous expression of gassericin A, a bacteriocin produced by Lactobacillus gasseri LA39. Anim Sci J 74:45–51

    Article  CAS  Google Scholar 

  • Kawai Y, Ishii Y, Arakawa K, Uemura K, Saitoh B, Nishimura J, Kitazawa H, Yamazaki Y, Tateno Y, Itoh T, Saitoh T (2004) Structural and functional differences in two cyclic bacteriocins with the same sequences produced by lactobacilli. Appl Environ Microbiol 70:2906–2911

    Article  CAS  Google Scholar 

  • Kawai Y, Kusnadi J, Kemperman R, Kok J, Ito Y, Endo M, Arakawa K, Uchida H, Nishimura J, Kitazawa H, Saito T (2009) DNA sequencing and homologous expression of a small peptide conferring immunity to gassericin A, a circular bacteriocin produced by Lactobacillus gasseri LA39. Appl Environ Microbiol 75:1324–1330

    Article  CAS  Google Scholar 

  • Kawulka K, Sprules T, McKay RT, Mercier P, Diaper CM, Zuber P, Vederas JC (2003) Structure of subtilosin A, an antimicrobial peptide from Bacillus subtilis with unusual posttranslational modifications linking cysteine sulfurs to α-carbons of phenylalanine and threonine. J Am Chem Soc 125:4726–4727

    Article  CAS  Google Scholar 

  • Kawulka KE, Sprules T, Diaper CM, Whittal RM, McKay RT, Mercier P, Zuber P, Vederas JC (2004) Structure of subtilosin A, a cyclic antimicrobial peptide from Bacillus subtilis with unusual sulfur to α-carbon cross-links: Formation and reduction of α-thio-α-amino acid derivatives. Biochemistry 43:3385–3395

    Article  CAS  Google Scholar 

  • Kemperman R, Jonker M, Nauta A, Kuipers OP, Kok J (2003a) Functional analysis of the gene cluster involved in production of the bacteriocin circularin A by Clostridium beijerinckii ATCC 25752. Appl Environ Microbiol 69:5839–5848

    Article  CAS  Google Scholar 

  • Kemperman R, Kuipers A, Karsens H, Nauta A, Kuipers O, Kok J (2003b) Identification and characterization of two novel clostridial bacteriocins, circularin A and closticin 574. Appl Environ Microbiol 69:1589–1597

    Article  CAS  Google Scholar 

  • Koglin A, Walsh CT (2009) Structural insights into nonribosomal peptide enzymatic assembly lines. Nat Prod Rep 26:987–1000

    Article  CAS  Google Scholar 

  • Krogh A, Larsson B, von Heijne G, Sonnhammer ELL (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305:567–580

    Article  CAS  Google Scholar 

  • Langdon GM, Bruix M, Gálvez A, Valdivia E, Maqueda M, Rico M (1998) Sequence-specific 1H assignment and secondary structure of the bacteriocin AS-48 cyclic peptide. J Biomol NMR 12:173–175

    Article  CAS  Google Scholar 

  • Leer RJ, van der Vossen JMBM, van Giezen M, van Noort JM, Pouwels PH (1995) Genetic analysis of acidocin B, a novel bacteriocin produced by Lactobacillus acidophilus. Microbiology 141:1629–1635

    Article  CAS  Google Scholar 

  • Maqueda M, Gálvez A, Martínez-Bueno M, Sanchez-Barrena MJ, González C, Albert A, Rico M, Valdivia E (2004) Peptide AS-48: prototype of a new class of cyclic bacteriocins. Curr Protein Pept Sci 5:399–416

    Article  CAS  Google Scholar 

  • Maqueda M, Sánchez-Hidalgo M, Fernández M, Montalbán-López M, Valdivia E, Martínez-Bueno M (2008) Genetic features of circular bacteriocins produced by Gram-positive bacteria. FEMS Microbiol Rev 32:2–22

    Article  CAS  Google Scholar 

  • Marahiel MA (2009) Working outside the protein-synthesis rules: insights into non-ribosomal peptide synthesis. J Pept Sci 15:799–807

    Article  CAS  Google Scholar 

  • Martínez-Bueno M, Gálvez A, Valdivia E, Maqueda M (1990) A transferable plasmid associated with AS-48 production in Enterococcus faecalis. J Bacteriol 172:2817–2818

    Google Scholar 

  • Martínez-Bueno M, Maqueda M, Gálvez A, Samyn B, Van Beeumen J, Coyette J, Valdivia E (1994) Determination of the gene sequence and the molecular structure of the enterococcal peptide antibiotic AS-48. J Bacteriol 176:6334–6339

    Google Scholar 

  • Martínez-Bueno M, Valdivia E, Gálvez A, Coyette J, Maqueda M (1998) Analysis of the gene cluster involved in production and immunity of the peptide antibiotic AS-48 in Enterococcus faecalis. Mol Microbiol 27:347–358

    Article  Google Scholar 

  • Martin-Visscher LA, van Belkum MJ, Garneau-Tsodikova S, Whittal RM, Zheng J, McMullen LM, Vederas JC (2008) Isolation and characterization of carnocyclin A, a novel circular bacteriocin produced by Carnobacterium maltaromaticum UAL307. Appl Environ Microbiol 74:4756–4763

    Article  CAS  Google Scholar 

  • Martin-Visscher LA, Gong XD, Duszyk M, Vederas JC (2009) The three-dimensional structure of carnocyclin a reveals that many circular bacteriocins share a common structural motif. J Biol Chem 284:28674–28681

    Article  CAS  Google Scholar 

  • Marx R, Stein T, Entian KD, Glaser SJ (2001) Structure of the Bacillus subtilis peptide antibiotic subtilosin A determined by 1H-NMR and matrix assisted laser desorption/ionization time-of-fight mass spectrometry. J Protein Chem 20:501–506

    Article  CAS  Google Scholar 

  • Miteva M, Andersson M, Karshikoff A, Otting G (1999) Molecular electroporation: a unifying concept for the description of membrane pore formation by antibacterial peptides, exemplified with NK-lysin. FEBS Lett 462:155–158

    Article  CAS  Google Scholar 

  • Montalbán-López M, Spolaore B, Pinato O, Martínez-Bueno M, Valdivia E, Maqueda M, Fontana A (2008) Characterization of linear forms of the circular enterocin AS-48 obtained by limited proteolysis. FEBS Lett 582:3237–3242

    Article  Google Scholar 

  • Nes IF, Diep DB, Holo H (2007a) Bacteriocin diversity in Streptococcus and Enterococcus. J Bacteriol 189:1189–1198

    Article  CAS  Google Scholar 

  • Nes IF, Yoon SS, Diep WB (2007b) Ribosomally synthesiszed antimicrobial peptides (Bacteriocins) in lactic acid bacteria: A review. Food Sci Biotechnol 16:675–690

    CAS  Google Scholar 

  • Oman TJ, van der Donk WA (2010) Follow the leader: the use of leader peptides to guide natural product biosynthesis. Nat Chem Biol 6:9–18

    Article  CAS  Google Scholar 

  • Rosengren KJ, Clark RJ, Daly NL, Göransson U, Jones A, Craik DJ (2003) Microcin J25 has a threaded sidechain-to-backbone ring structure and not a head-to-tail cyclized backbone. J Am Chem Soc 125:12464–12474

    Article  CAS  Google Scholar 

  • Salomón RA, Farías RN (1992) Microcin-25, a novel antimicrobial peptide produced by Escherichia coli. J Bacteriol 174:7428–7435

    Google Scholar 

  • Samyn B, Martínez-Bueno M, Devreese B, Maqueda M, Gálvez A, Valdivia E, Coyette J, Van Beeumen J (1994) The cyclic structure of the enterococcal peptide antibiotic AS-48. FEBS Lett 352:87–90

    Article  CAS  Google Scholar 

  • Sánchez-Barrena MJ, Martínez-Ripoll M, Gálvez A, Valdivia E, Maqueda M, Cruz V, Albert A (2003) Structure of bacteriocin AS-48: from soluble state to membrane bound state. J Mol Biol 334:541–549

    Article  Google Scholar 

  • Saska I, Gillon AD, Hatsugai N, Dietzgen RG, Hara-Nishimura I, Anderson MA, Craik DJ (2007) An asparaginyl endopeptidase mediates in vivo protein backbone cyclization. J Biol Chem 282:29721–29728

    Article  CAS  Google Scholar 

  • Sawa N, Zendo T, Kiyofuji J, Fujita K, Himeno K, Nakayama J, Sonomoto K (2009) Identification and characterization of lactocyclicin Q, a novel cyclic bacteriocin produced by Lactococcus sp. strain QU 12. Appl Environ Microbiol 75:1552–1558

    Article  CAS  Google Scholar 

  • Shelburne CE, An FY, Dholpe V, Ramamoorthy A, Lopatin DE, Lantz MS (2007) The spectrum of antimicrobial activity of the bacteriocin subtilosin A. J Antimicrob Chemother 59:297–300

    Article  CAS  Google Scholar 

  • Silkin L, Hamza S, Kaufman S, Cobb SL, Vederas JC (2008) Spermicidal bacteriocins: Lacticin 3147 and subtilosin A. Bioorg Med Chem Lett 18:3103–3106

    Article  CAS  Google Scholar 

  • Thennarasu S, Lee DK, Poon A, Kawulka KE, Vederas JC, Ramamoorthy A (2005) Membrane permeabilization, orientation, and antimicrobial mechanism of subtilosin A. Chem Phys Lipids 137:38–51

    Article  CAS  Google Scholar 

  • Toba T, Samant SK, Yoshioka E, Itoh T (1991) Reutericin 6, a new bacteriocin produced by Lactobacillus reuteri LA6. Lett Appl Microbiol 13:281–286

    Article  CAS  Google Scholar 

  • van Belkum MJ, Stiles ME (2000) Nonlantibiotic antibacterial peptides from lactic acid bacteria. Nat Prod Rep 17:323–335

    Article  Google Scholar 

  • van Belkum MJ, Worobo RW, Stiles ME (1997) Double-glycine-type leader peptides direct secretion of bacteriocins by ABC transporters: colicin V secretion in Lactococcus lactis. Mol Microbiol 23:1293–1301

    Article  Google Scholar 

  • Walsh CT (2004) Polyketide and nonribosomal peptide antibiotics: modularity and versatility. Science 303:1805–1810

    Article  CAS  Google Scholar 

  • Wilson KA, Kalkum M, Ottesen J, Yuzenkova J, Chait BT, Landick R, Muir T, Severinov K, Darst SA (2003) Structure of microcin J25, a peptide inhibitor of bacterial RNA polymerase, is a lassoed tail. J Am Chem Soc 125:12475–12483

    Article  CAS  Google Scholar 

  • Wirawan RE, Swanson KM, Kleffmann T, Jack RW, Tagg JR (2007) Uberolysin: a novel cyclic bacteriocin produced by Streptococcus uberis. Microbiology 153:1619–1630

    Article  CAS  Google Scholar 

  • Zheng G, Yan LZ, Vederas JC, Zuber P (1999) Genes of the sbo-alb locus of Bacillus subtilis are required for production of the antilisterial bacteriocin subtilosin. J Bacteriol 181:7346–7355

    CAS  Google Scholar 

  • Zheng GL, Hehn R, Zuber P (2000) Mutational analysis of the sbo-alb locus of Bacillus subtilis: identification of genes required for subtilosin production and immunity. J Bacteriol 182:3266–3273

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Alberta, Edmonton, AB, Canada, T6G 2G2

    John C. Vederas

Authors
  1. Leah A. Martin-Visscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco J. van Belkum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John C. Vederas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John C. Vederas .

Editor information

Editors and Affiliations

  1. Nantes-Atlantic Natl. College of Vet. Me, Food Sci. & Eng., ONIRIS, Nantes, France

    Djamel Drider

  2. Dépt. Régulations, Développement et, Diversité Moléculaire, Muséum National d'Histoire Naturelle, rue Cuvier 57, Paris, 75005, France

    Sylvie Rebuffat

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Martin-Visscher, L.A., van Belkum, M.J., Vederas, J.C. (2011). Class IIc or Circular Bacteriocins. In: Drider, D., Rebuffat, S. (eds) Prokaryotic Antimicrobial Peptides. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7692-5_12

Download citation

Publish with us

Policies and ethics

Search

Navigation