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Journal ArticleDOI

Lactococcal bacteriocins - mode of action and immunity

01 Aug 1995-Trends in Microbiology (ELSEVIER SCI LTD)-Vol. 3, Iss: 8, pp 299-304
TL;DR: The lactococcal bacteriocins are hydrophobic cationic peptides, which form pores in the cytoplasmic membrane of sensitive cells.
About: This article is published in Trends in Microbiology.The article was published on 1995-08-01 and is currently open access. It has received 78 citations till now. The article focuses on the topics: Bacteriocin & Antimicrobial peptides.

Summary (2 min read)

Lactococcal bacteriocins: mode of action and immunitv

  • It is tempting to assume that different strains of a species produce these substances to enable them to compete for the same ecological niche.
  • Class I bacteriocins, or lantibiotics, are small membrane-active peptides that contain the unusual amino acids lanthionine, P-methyllanthionine, dehydroalanine and dehydrobutyrine.
  • All the lactococcal bacteriocins that have been thoroughly characterized so far belong to class I or II.

Mode of action of lantlbiotics: nisin

  • Nisin is the only lantibiotic produced by L. luctis for which the mode of action has been studied.
  • It is active against a broad spectrum of Gram-positive bacteria; Escherichia coli and other Gram-negative bacteria are only affected when their outer membranes are weakened or disrupted by treatment with EDTA or osmotic shock21,22, which makes their inner membrane accessible to the lantibiotic.

REVIEWS

  • Nisin has a dual activity against spore-forming bacteria: it inhibits the outgrowth of spores and kills cells in the vegetative state.
  • The 2,3_didehydroamino acid residues in nisin are thought to act against spores by interacting with the membrane sulfhydryl groups of germinating spores 23.
  • It dissipates the membrane potential of whole cells, cytoplasmic membrane vesicles and artificial membrane vesicles ( liposomes)24125, indicating that the peptide does not require a specific receptor protein for activity or for membrane insertion.
  • Membrane disruption is believed to result from the incorporation of nisin into the cytoplasmic membrane to form an ion channel or pore.
  • This may account for the differences in sensitivity seen be-tween bacterial species or strains, as permeabilization only occurs in liposomes that contain zwitterionic phospholipids28T2p.

Mode of action of non-Iantibiotics Diplococcin

  • The effect of purified diplococcin from L. lactis subsp.
  • The addition of 8 arbitrary units of diplococcin to sensitive cells completely abolishes DNA and RNA synthesis within 2 min, which may partially interrupt protein synthesis.
  • Small pores allow leakage of protons and other small ions only, whereas amino acids leak through larger pores.
  • No receptor is required for nisin activity.

Lactostrepcin 5

  • Lactostrepcin 5 (Las.5) and other lactostrepcins have a strong and rapid bactericidal effect on sensitive cells33; only Las5 has been characterized in detail.
  • It inhibits uridine uptake and causes leakage of K+ ions and ATP from cells.
  • Like diplococcin, Las5 inhibits DNA, RNA and protein synthesis, probably by the inhibition of transport of precursors required for macromolecular synthesis, energy depletion of the cell and/or leakage from the cell of small solutes that are required for various metabolic activities.
  • Las5 is equally active against energized and energy-depleted cells33.

Lactococcins A and B

  • They belong to a group of small, cationic hydrophobic peptides (including several lantibiotics) that permeabilize membranes28934"6.
  • The mode of action of purified lactococcin A has been studied using whole cells of sensitive lactococcal strains and membrane vesicles made from such cells, and also using liposomes obtained from lactococcal phospholipids3'.
  • Similar studies on whole cells have also been done using partially purified lactococcin B (Ref. 38) .
  • These results indicate that both lactococcins form pores in the cytoplasmic membrane in a voltage-independent manner.
  • Low concentrations of lactococcin B allow leakage of protons and ions, whereas ISO-fold more bacteriocin is needed for leakage of glutamate to occur38, which indicates that pores of different sizes can exist.

Nisin immunity and resistance

  • There are several mechanisms by which bacteria protect themselves against nisin.
  • Nisin resistance (Nis') is not genetically linked to nisin production.
  • These results have been united in a model for LciA topology (Fig. 3b ).
  • Residues 29-47 are considered to span the cytoplasmic membrane as an amphiphilic a helix by interacting with another transmembrane protein, possibly the lactococcin A receptor.

Conclusions and perspectives

  • The past few years have seen significant progress in their understanding of nisin and the lactococcins.
  • The structural and immunity genes and the genes encoding the secretion and post-translational modification machinery have been cloned, and the authors are now beginning to understand the modes of action of nisin and the lactococcins A and B, and the way in which the lactococcin A immunity protein LciA works.
  • This knowledge, combined with structure-function studies of the bacteriocins, should allow the construction of molecules with enhanced or altered activities and broader specificities for use as, for example, food preservatives.
  • A tropism for the mucous membranes of the human respiratory tract; indeed, the upper respiratory tract of humans is virtually the sole reservoir for this organism.
  • Infection by H. in/kenzae illustrates the complex interplay that can occur between the host and the pathogen, in a relationship that does not always culminate in disease4.

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Citations
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Journal ArticleDOI
TL;DR: Toxicity data exist for only a few bacteriocins, but research and their long-time intentional use strongly suggest that bacteriOCins can be safely used.

1,782 citations


Cites background from "Lactococcal bacteriocins - mode of ..."

  • ...The Ž .lactococcin A immunity protein LcnI is by far the most studied one, yet the basic mechanism behind Žthe immunity is still not understood Nissen-Meyer .et al., 1993; Venema et al., 1994, 1995 ....

    [...]

Journal ArticleDOI
TL;DR: The role of lactic acid bacteria in many such fermentations and the mechanisms of antibiosis with particular reference to bacteriocins are outlined and a brief description of some important fermented foods from various countries are given.

1,013 citations

Journal ArticleDOI
TL;DR: The present review attempts to provide an insight into general knowledge available for class IIa bacteriocins and discusses common features and recent findings concerning these substances.
Abstract: In the last decade, a variety of ribosomally synthesized antimicrobial peptides or bacteriocins produced by lactic acid bacteria have been identified and characterized. As a result of these studies, insight has been gained into fundamental aspects of biology and biochemistry such as producer self protection, membrane-protein interactions, and protein modification and secretion. Moreover, it has become evident that these peptides may be developed into useful antimicrobial additives. Class IIa bacteriocins can be considered as the major subgroup of bacteriocins from lactic acid bacteria, not only because of their large number, but also because of their activities and potential applications. They have first attracted particular attention as listericidal compounds and are now believed to be the next in line if more bacteriocins are to be approved in the future. The present review attempts to provide an insight into general knowledge available for class IIa bacteriocins and discusses common features and recent findings concerning these substances.

611 citations


Cites background from "Lactococcal bacteriocins - mode of ..."

  • ...Class IIa bacteriocins are generally opposed to nisin in the sense that they interact with the cytoplasmic membranes of sensitive cells regardless of their degree of prior energization, suggesting that the loss of permeability of the cytoplasmic membrane occurs in a voltage-independent manner [3,49,85,86], while nisin acts in a membrane-potential-dependent manner [5,92]....

    [...]

  • ...The initial step of class-IIa-bacteriocin interaction with the membrane surface is generally believed to be an electrostatic binding mediated by a putative membrane-bound receptor-type molecule [28,49,86]....

    [...]

  • ...The lethal activity of class IIa bacteriocins is thus mainly ascribed to the dissipation of the PMF [3,28,49]....

    [...]

Journal ArticleDOI
TL;DR: This review article focuses primarily on class I and class IIa bacteriocins produced by lactic acid bacteria (LAB) given their development as food preservatives.
Abstract: Over the last 2 decades, a variety of bacteriocins, produced by bacteria that kill or inhibit the growth of other bacteria, have been identified and characterized biochemically and genetically. This review article focuses on the ecology of bacteriocins, determination of bacteriocin activity, biosynthesis of bacteriocins, and mode of action. Bacteriocin production and modeling are discussed in the article. Nisin is discussed in some detail in this article since it is currently the only purified bacteriocin approved for food use in the U.S. and has been successfully used for several decades as a food preservative in more than 50 countries. For activity spectra and food applications, the review article focuses primarily on class I and class IIa bacteriocins produced by lactic acid bacteria (LAB) given their development as food preservatives.

502 citations

Journal ArticleDOI
TL;DR: Although today a lot is known about LAB bacteriocins and the regulation of their production, several fundamental questions remain to be solved, including questions regarding mechanisms of immunity and resistance, as well as the molecular basis of target-cell specificity.
Abstract: Lactic acid bacteria (LAB) fight competing Gram-positive microorganisms by secreting anti-microbial peptides called bacteriocins. Peptide bacteriocins are usually divided into lantibiotics (class I) and non-lantibiotics (class II), the latter being the main topic of this review. During the past decade many of these bacteriocins have been isolated and characterized, and elements of the genetic mechanisms behind bacteriocin production have been unravelled. Bacteriocins often have a narrow inhibitory spectrum, and are normally most active towards closely related bacteria likely to occur in the same ecological niche. Lactic acid bacteria seem to compensate for these narrow inhibitory spectra by producing several bacteriocins belonging to different classes and having different inhibitory spectra. The latter may also help in counteracting the possible development of resistance mechanisms in target organisms. In many strains, bacteriocin production is controlled in a cell-density dependent manner, using a secreted peptide-pheromone for quorum-sensing. The sensing of its own growth, which is likely to be comparable to that of related species, enables the producing organism to switch on bacteriocin production at times when competition for nutrients is likely to become more severe. Although today a lot is known about LAB bacteriocins and the regulation of their production, several fundamental questions remain to be solved. These include questions regarding mechanisms of immunity and resistance, as well as the molecular basis of target-cell specificity.

363 citations


Cites background from "Lactococcal bacteriocins - mode of ..."

  • ...This may be taken to indicate that immunity proteins act via an effect on a (putative) bacteriocin receptor in the cytoplasmic membrane (e.g. Venema et al. 1995)....

    [...]

  • ...Venema et al. (1995) showed that the C-terminal part of the lactococcin A immunity protein is exposed to the exterior of the cell....

    [...]

  • ...This may be taken to indicate that immunity proteins act via an effect on a (putative) bacteriocin receptor in the cytoplasmic membrane (e.g. Venema et al. 1995 )....

    [...]

  • ... Venema et al. (1995) showed that the C-terminal part of the lactococcin A immunity protein is exposed to the exterior of the cell....

    [...]

  • ...…indicate that immunity proteins for class II bacteriocins are soluble and mainly located in the cytoplasm, although in some cases the presence of one transmembrane helix has been suggested (Nissen-Meyer et al. 1993; Quadri et al. 1995; Venema et al. 1995; Dayem et al. 1996; Eijsink et al. 1998)....

    [...]

References
More filters
Journal ArticleDOI
TL;DR: An atypical Leuconostoc paramesenteroides strain isolated from retail lamb produced a bacteriocin, leuconocin S, that was inactivated by alpha-amylase, trypsin, alpha-chymotrypsIn, protease, and proteinase K but not by lipase or heat treatment at 60 degrees C for 30 min.
Abstract: An atypical Leuconostoc paramesenteroides strain isolated from retail lamb produced a bacteriocin, leuconocin S, that was inactivated by α-amylase, trypsin, α-chymotrypsin, protease, and proteinase K but not by lipase or heat treatment at 60°C for 30 min. Supernatants from culture broths produced two glycoprotein bands on sodium dodecyl sulfate-polyacrylamide gels; these had molecular weights of 2,000 and 10,000 and activity against Lactobacillus sake ATCC 15521. The crude bacteriocin preparation was bacteriostatic and dissipated proton motive force. Bacteriocin activity was produced over a wide pH range (5.2 to 7.9) on buffered agar medium, with an optimum pH of pH 6.15. The optimum pH for production in broth was 6.5 to 7.0. Images

132 citations

Book
01 Dec 1992
TL;DR: Genetic determinants for microcin H47, an Escherichia coli chromosome-encoded antibiotic and the three-dimensional structure of nisin in aqueous solution are presented.
Abstract: to the Microcin Session.- Escherichia coli genes regulating the production of microcins MCCB17 and MCCC7.- Uptake and mode of action of the peptide antibiotic microcin B17.- The structure and maturation pathway of microcin B17.- Bacteriocins of Gram-positive bacteria: an opinion regarding their nature, nomenclature and numbers.- Molecular properties of Lactobacillus bacteriocins.- Lactococcal bacteriocins: genetics and mode of action.- to the Lantibiotics session.- Lantibiotics : An overview and conformational studies on Gallidermin and Pep5.- Biosynthesis of the lantibiotic Pep5 and mode of action of type A lantibiotics.- Identification of genes involved in lantibiotic synthesis.- Pore forming bacteriocins.- In vivo properties of colicin A: channel activity and translocation.- Site-directed fluorescence spectroscopy as a tool to study the membrane insertion of colicin A.- Structure-function of the colicin E1 ion channel: voltage-driven translocation and gating of a tetra- (or hexa-) helix channel.- Voltage-dependent gating of colicin E1 channels in planar bilayers.- Immunity to colicins.- Immunity protein to pore forming colicins.- Specificity determinants for the interaction of colicin E9 with its immunity protein.- Structural studies on colicin E3 and its immunity protein.- Study of the import mechanisms of colicins through protein engineering and K+ efflux kinetics.- Import and export of colicin M.- TolA: structure, location and role in the uptake of colicins.- Domains of the Escherichia coli BtuB protein involved in outer membrane association and interaction with colicin translocation components.- A structure-function analysis of BtuB, the E.coli vitamin B12 outer membrane transport protein.- General introduction to the secretion of bacteriocins.- Functioning of the pCloDF13 encoded BRP.- Structure/function relationships in the signal sequence of the colicin A lysis protein.- The secretion of colicin V.- to the session on the evolution of bacteriocins.- Molecular evolution of E colicin plasmids with emphasis on the endonuclease types.- Immunity specificity and evolution of the nuclease-type E colicins.- Replicon evolution of ColE2-related plasmids.- Manuscripts of poster presentations.- Genetic determinants for microcin H47, an Escherichia coli chromosome-encoded antibiotic.- BLIS production in the genus Streptococcus.- A new Leuconostoc bacteriocin, Mesentericin Y105, bactericidal to Listeria monocytogenes.- Cloning and characterisation of a lysin gene from a Listeria bacteriophage.- Transformation of Enterococcus faecalis OGIX with the plasmid pMB2 encoding for the peptide antibiotic AS-48, by protoplast fusion and regeneration on calcium alginate.- NMR studies of lantibiotics: the three-dimensional structure of nisin in aqueous solution.- Localization and phenotypic expression of genes involved in the biosynthesis of the Lactococcus lactis subsp. lactis lantibiotic nisin.- Expression of nisin in Bacillus subtllis.- Tn5301, a Lactococcal transposon encoding genes for nisin biosynthesis.- Development of yeast inhibitory compounds for incorporation into silage inoculants.- The excC and excD genes of Escherichia coli K-12 encode the peptidoglycan-associated lipoprotein (PAL) and the TolQ protein, respectively.- Resistance and tolerance of bacteria to E colicins.- Construction and characterization of chimeric proteins between pyocins and colicin E3.- Colicins as anti-tumour drugs.- List of Participants.

127 citations

Journal ArticleDOI
TL;DR: Uptake and efflux studies of different solutes suggest that LcnB forms pores in the cytoplasmic membrane of sensitive L. lactis cells in the absence of a proton motive force.
Abstract: Lactococcin B (LcnB) is a small, hydrophobic, positively charged bacteriocin produced by Lactococcus lactis subsp. cremoris 9B4. Purified LcnB has a bactericidal effect on sensitive L. lactis cells by dissipating the proton motive force and causing leakage of intracellular substrates. The activity of LcnB depends on the reduced state of the Cys-24 residue. Uptake and efflux studies of different solutes suggest that LcnB forms pores in the cytoplasmic membrane of sensitive L. lactis cells in the absence of a proton motive force. At low concentrations of LcnB, efflux of those ions and amino acids which are taken up by proton motive force-driven systems was observed. However, a 150-fold higher LcnB concentration was required for efflux of glutamate, previously taken up via a unidirectional ATP-driven transport system. Strains carrying the genetic information for the immunity protein against LcnB were not affected by LcnB. The proton motive force of immune cells was not dissipated, and no leakage of intracellular substrates could be detected.

122 citations

Journal ArticleDOI
TL;DR: Succinylation of the lysine residues of Pep 5 resulted in prolonged pore lifetimes and maintenance of distinct conductance levels, which is probably the reason for the reduced activity of the modified peptide against intact gram-positive bacteria.
Abstract: The cationic staphylococcinlike peptide Pep 5 is shown to depolarize bacterial and planar lipid membranes in a voltage-dependent manner. An artificial valinomycin-induced potassium diffusion potential across the cytoplasmic membrane of Staphylococcus cohnii 22 was sufficient to promote Pep 5 action. Thus, evidence is provided that a membrane potential of sufficient magnitude is the only prerequisite for Pep 5 activity. The voltage dependence was elucidated by macroscopic conductance measurements with black lipid membranes. A threshold potential of about -90 to -100 mV, which was deduced from experiments with bacterial cells, could be confirmed. Single pores were resolved which often occur as short-lived bursts and fluctuate among different conductance levels. Pore diameters were calculated ranging from 0.1 to 1 nm. Succinylation of the lysine residues of Pep 5 resulted in prolonged pore lifetimes and maintenance of distinct conductance levels. However, the succinylated peptide required a higher threshold potential, approximately -150 mV, than the native peptide, which is probably the reason for the reduced activity of the modified peptide against intact gram-positive bacteria.

121 citations

Journal Article
TL;DR: At least six different modes of colicin action have been identified, and it is still not clear whether Colicinogeny is advantageous in natural environments.
Abstract: At least six different modes of colicin action have been identified. Plasmids encoding colicins also confer specific colicin immunity upon their host cells, thereby protecting them against the action of their own colicin. It is still not clear whether colicinogeny is advantageous in natural environments.

109 citations