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Bacteriocins are proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally, and ecologically diverse. Applications of bacteriocins are being tested to assess their application as narrow-spectrum antibiotics.[1]

Lactococcin-like family
Symbol Lactococcin
Pfam PF04369
Pfam clan CL0400
InterPro IPR007464
TCDB 1.C.22
Bacteriocin (Lactococcin_972)
Symbol Lactococcin_972
Pfam PF09683
InterPro IPR006540

Bacteriocins were first discovered by André Gratia in 1925.[2][3] He was involved in the process of searching for ways to kill bacteria, which also resulted in the development of antibiotics and the discovery of bacteriophage, all within a span of a few years. He called his first discovery a colicine because it killed E. coli.


Classification of bacteriocinsEdit

Bacteriocins are categorized in several ways, including producing strain, common resistance mechanisms, and mechanism of killing. There are several large categories of bacteriocin which are only phenomenologically related. These include the bacteriocins from gram-positive bacteria, the colicins,[4] the microcins, and the bacteriocins from Archaea. The bacteriocins from E. coli are called colicins (formerly called 'colicines,' meaning 'coli killers'). They are the longest studied bacteriocins. They are a diverse group of bacteriocins and do not include all the bacteriocins produced by E. coli. In fact, one of the oldest known so-called colicins was called colicin V and is now known as microcin V. It is much smaller and produced and secreted in a different manner than the classic colicins.

This naming system is problematic for a number of reasons. First, naming bacteriocins by what they putatively kill would be more accurate if their killing spectrum were contiguous with genus or species designations. The bacteriocins frequently possess spectra that exceed the bounds of their named taxa and almost never kill the majority of the taxa for which they are named. Further, the original naming is generally derived not from the sensitive strain the bacteriocin kills, but instead the organism that produces the bacteriocin. This makes the use of this naming system a problematic basis for theory; thus the alternative classification systems.

Bacteriocins that contain the modified amino acid lanthionine as part of their structure are called lantibiotics. However, efforts to reorganize the nomenclature of the family of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products have led to the differentiation of lantipeptides from bacteriocins based on biosynthetic genes.[5]

Methods of classificationEdit

Alternative methods of classification include: method of killing (pore-forming, nuclease activity, peptidoglycan production inhibition, etc.), genetics (large plasmids, small plasmids, chromosomal), molecular weight and chemistry (large protein, peptide, with/without sugar moiety, containing atypical amino acids such as lanthionine), and method of production (ribosomal, post-ribosomal modifications, non-ribosomal).

Bacteriocins from Gram negative bacteriaEdit

Gram negative bacteriocins are typically classified by size. Microcins are less than 20 kDa in size, colicin-like bacteriocins are 20 to 90 kDa in size and tailocins or so called high molecular weight bacteriocins which are multi subunit bacteriocins that resemble the tails of bacteriophages. This size classification also coincides with genetic, structural and functional similarities.


See main article on microcins.

Colicin-like bacteriocinsEdit

Colicins are bacteriocins (CLBs) found in the Gram-negative E. coli. Similar bacteriocins occur in other Gram-negative bacteria. These CLBs are distinct from Gram-positive bacteriocins. They are modular proteins between 20 and 90 kDa in size. They often consist of a receptor binding domain, a translocation domain and a cytotoxic domain. Combinations of these domains between different CLBs occur frequently in nature and can be created in the laboratory. Due to these combinations further subclassifaction can be based on either import mechanism (group A and B) or on cytotoxic mechanism (nucleases, pore forming, M-type, L-type).[6]


Most well studied are the tailocins of Pseudomonas aeruginosa. They can be further subdivided into R-type and F-type pyocins.[7]

Bacteriocins from Gram positive bacteriaEdit

Bacteriocins from Gram positive bacteria are typically classified into Class I, Class IIa/b/c, and Class III. [8]

Class I bacteriocinsEdit

The class I bacteriocins are small peptide inhibitors and include nisin and other lantibiotics.

Class II bacteriocinsEdit

The class II bacteriocins are small (<10 kDa) heat-stable proteins. This class is subdivided into five subclasses. The class IIa bacteriocins (pediocin-like bacteriocins) are the largest subgroup and contain an N-terminal consensus sequence -Tyr-Gly-Asn-Gly-Val-Xaa-Cys across this group. The C-terminal is responsible for species-specific activity, causing cell-leakage by permeabilizing the target cell wall.

Class IIa bacteriocins have a large potential for use in food preservation as well medical applications due to their strong anti-Listeria activity and broad range of activity. One example of Class IIa bacteriocin is pediocin PA-1.[9]
The class IIb bacteriocins (two-peptide bacteriocins) require two different peptides for activity. One such an example is lactococcin G, which permeabilizes cell membranes for monovalent sodium and potassium cations, but not for divalent cations. Almost all of these bacteriocins have a GxxxG motifs. This motif is also found in transmembrane proteins, where they are involved in helix-helix interactions. Accordingly, the bacteriocin GxxxG motifs can interact with the motifs in the membranes of the bacterial cells, killing the cells.[10]
Class IIc encompasses cyclic peptides, in which the N-terminal and C-terminal regions are covalentely linked. Enterocin AS-48 is the prototype of this group.
Class IId cover single-peptide bacteriocins, which are not post-translationally modified and do not show the pediocin-like signature. The best example of this group is the highly stable aureocin A53. This bacteriocin is stable under highly acidic conditions, high temperatures, and is not affected by proteases.[11]

The most recently proposed subclass is the Class IIe, which encompasses those bacteriocins composed by three or four non-pediocin like peptides. The best example is aureocin A70, a four-peptide bacteriocin, highly active against Listeria monocytogenes, with potential biotechnological applications.[12]

Class III bacteriocinsEdit

Class III bacteriocins are large, heat-labile (>10 kDa) protein bacteriocins. This class is subdivided in two subclasses: subclass IIIa or bacteriolysins and subclass IIIb. Subclass IIIa comprises those peptides that kill bacterial cells by cell wall degradation, thus causing cell lysis. The best studied bacteriolysin is lysostaphin, a 27 kDa peptide that hydrolises the cell walls of several Staphylococcus species, principally S. aureus.[13] Subclass IIIb, in contrast, comprises those peptides that do not cause cell lysis, killing the target cells by disrupting the membrane potential, which causes ATP efflux .

Class IV bacteriocinsEdit

Class IV bacteriocins are defined as complex bacteriocins containing lipid or carbohydrate moieties. Confirmation by experimental data was established with the characterisation of sublancin and glycocin F (GccF) by two independent groups.[14][15]


Two databases of bacteriocins are available: BAGEL[16] and BACTIBASE.[17][18]

Medical significanceEdit

Bacteriocins are of interest in medicine because they are made by non-pathogenic bacteria that normally colonize the human body. An example of this would be genus Lactobacilli. These bacteria inhabit the normal, lower reproductive tract of women.[19] Loss of these harmless bacteria following antibiotic use may allow opportunistic pathogenic bacteria to invade the human body.[citation needed]

Bacteriocins have also been suggested as a cancer treatment.[20][21] They have shown distinct promise as a diagnostic agent for some cancers,[22][23][24][25][26] but their status as a form of therapy remains experimental and outside the mainstream of cancer research. This is partly due to questions about their mechanism of action and the presumption that anti-bacterial agents have no obvious connection to killing mammalian tumor cells. Some of these questions have been addressed, at least in part.[27][28]

Bacteriocins[which?] were tested as AIDS drugs around 1990, but did not progress beyond in-vitro tests on cell lines.[29]

Bacteriocins have been proposed as a replacement for antibiotics to which pathogenic bacteria have become resistant. Potentially, the bacteriocins could be produced by bacteria intentionally introduced into the patient to combat infection.[30]

In spite of these promising advantages, nisin is the only bacteriocin generally recognized as safe by the Food and Drug Administration and is currently used as a food preservative in several countries.This limitation in bacteriocins availability in the market as preservatives and antimicrobials can be attributed to multiple factors, including: (i) the high cost of their commercial production; (ii) the loss of their activity by proteolytic enzymes; (iii) their unfavorable interactions with other food constituents, which decreases the availability and necessitates a huge amount of the peptide to be added; (iv) the alterations of the chemical and physical properties of these compounds during the various food-processing stages; (v) the low yield of these compounds due to ineffective recovery by traditional purification methods; and (vi) the narrow spectrum of activity observed for most of the tested bacteriocins against pathogenic bacteria. In the last years, several studies on bacteriocins have demonstrated that the optimization of their production conditions, their purification methods, their combinations with other antimicrobial agents, the hurdle technology approach, and nanotechnology formulations, could all represent solutions to some of the previously mentioned problems.[31]


There are many ways to demonstrate bacteriocin production, depending on the sensitivity and labor intensiveness desired. To demonstrate their production, technicians stab inoculate multiple strains on separate multiple nutrient agar Petri dishes, incubate at 30 °C for 24 h., overlay each plate with one of the strains (in soft agar), incubate again at 30 °C for 24 h. After this process, the presence of bacteriocins can be inferred if there are zones of growth inhibition around stabs. This is the simplest and least sensitive way. It will often mistake phage for bacteriocins. Some methods prompt production with UV radiation, Mitomycin C, or heat shock. UV radiation and Mitomycin C are used because the DNA damage they produce stimulates the SOS response. Cross streaking may be substituted for lawns. Similarly, production in broth may be followed by dripping the broth on a nascent bacterial lawn, or even filtering it. Precipitation (ammonium sulfate) and some purification (e.g. column or HPLC) may help exclude lysogenic and lytic phage from the assay.

Bacteriocins by nameEdit

  • acidocin
  • actagardine
  • agrocin
  • alveicin
  • aureocin
  • aureocin A53
  • aureocin A70
  • bisin
  • carnocin
  • carnocyclin
  • caseicin
  • cerein[32]
  • circularin A[33]
  • colicin
  • curvaticin
  • divercin
  • duramycin
  • enterocin
  • enterolysin
  • epidermin/gallidermin
  • erwiniocin
  • gardimycin
  • gassericin A[34]
  • glycinecin
  • halocin
  • haloduracin
  • klebicin
  • lactocin S[35]
  • lactococcin
  • lacticin
  • leucoccin
  • lysostaphin
  • macedocin
  • mersacidin
  • mesentericin
  • microbisporicin
  • microcin S
  • mutacin
  • nisin
  • paenibacillin
  • planosporicin
  • pediocin
  • pentocin
  • plantaricin
  • pneumocyclicin[36]
  • pyocin[37]
  • reutericin 6[38]
  • sakacin
  • salivaricin[39]
  • sublancin
  • subtilin
  • sulfolobicin
  • tasmancin[40]
  • thuricin 17
  • trifolitoxin
  • variacin
  • vibriocin
  • warnericin
  • warnerin

See alsoEdit


  1. ^ Cotter, Paul D.; Ross, R. Paul; Hill, Colin (2012). "Bacteriocins — a viable alternative to antibiotics?". Nature Reviews Microbiology. 11 (2): 95–105. doi:10.1038/nrmicro2937. ISSN 1740-1526. 
  2. ^ Gratia A (1925). "Sur un remarquable example d'antagonisme entre deux souches de colibacille". Compt. Rend. Soc. Biol. 93: 1040–2. 
  3. ^ Gratia JP (October 2000). "André Gratia: a forerunner in microbial and viral genetics". Genetics. 156 (2): 471–6. PMC 1461273 . PMID 11014798. 
  4. ^ Cascales E, Buchanan SK, Duché D, et al. (March 2007). "Colicin Biology". Microbiol. Mol. Biol. Rev. 71 (1): 158–229. doi:10.1128/MMBR.00036-06. PMC 1847374 . PMID 17347522. 
  5. ^ Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J, Cotter PD, Craik DJ, Dawson M, Dittmann E, Donadio S, Dorrestein PC, Entian KD, Fischbach MA, Garavelli JS, Göransson U, Gruber CW, Haft DH, Hemscheidt TK, Hertweck C, Hill C, Horswill AR, Jaspars M, Kelly WL, Klinman JP, Kuipers OP, Link AJ, Liu W, Marahiel MA, Mitchell DA, Moll GN, Moore BS, Müller R, Nair SK, Nes IF, Norris GE, Olivera BM, Onaka H, Patchett ML, Piel J, Reaney MJ, Rebuffat S, Ross RP, Sahl HG, Schmidt EW, Selsted ME, Severinov K, Shen B, Sivonen K, Smith L, Stein T, Süssmuth RD, Tagg JR, Tang GL, Truman AW, Vederas JC, Walsh CT, Walton JD, Wenzel SC, Willey JM, van der Donk WA (2013). "Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature". Nat Prod Rep. 30 (1): 108–60. doi:10.1039/c2np20085f. PMC 3954855 . PMID 23165928. 
  6. ^ Eric Cascales and others, ‘Colicin Biology’, MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 71.1 (2007), 158–229 <>.
  7. ^ Maarten G K Ghequire and René De Mot, ‘Ribosomally Encoded Antibacterial Proteins and Peptides from Pseudomonas’, FEMS Microbiology Reviews, 38.4 (2014), 523–68 <>.
  8. ^ Cotter PD, Hill C, Ross RP (2006). "What's in a name? Class distinction for bacteriocins". Nature Reviews Microbiology. 4 (2). doi:10.1038/nrmicro1273-c2.  is author reply to comment on article :Cotter PD, Hill C, Ross RP (2005). "Bacteriocins: developing innate immunity for food". Nature Reviews Microbiology. 3 (?): 777–88. doi:10.1038/nrmicro1273. PMID 16205711. 
  9. ^ HENG, C. K. N., WESCOMBE, P. A., BURTON, J. P., JACK, R. W., & TAGG, J. R. (2007). The diversity of bacteriocins in Gram-positive bacteria. In: Bacteriocins: Ecology and Evolution. 1st ed., Riley, M. A. & Chavan, M. A., Eds. Springer, Hildberg, p. 45-83.
  10. ^ Nissen-Meyer, J; Rogne, P; Oppegård, C; Haugen, HS; Kristiansen, PE (2013-08-12). "Structure-function relationships of the non-lanthionine-containing peptide (class II) bacteriocins produced by gram-positive bacteria". Curr Pharm Biotechnol. 10: 19–37. PMID 19149588. 
  11. ^ NETZ D. J., POHL , BECK-SICKINGER A. G., SELMER , PIERIK , SAHL H. G. (2002). "Biochemical characterisation and genetic analysis of aureocin A53, a new, atypical bacteriocin from Staphylococcus aureus". J. Mol. Biol. 319: 745–756. doi:10.1016/s0022-2836(02)00368-6. PMID 12054867. 
  12. ^ NETZ D. J. A., SAHL , NASCIMENTO , OLIVEIRA , SOARES , BASTOS M. C. F. (2001). "Molecular characterisation of aureocin A70, a multiple-peptide bacteriocin isolated from Staphylococcus aureus". J. Mol. Biol. 311: 939–949. doi:10.1006/jmbi.2001.4885. 
  13. ^ Bastos M.C.F., Coutinho B.G., Coelho M.L.V. Lysostaphin: A Staphylococcal Bacteriolysin with Potential Clinical Applications. Pharmaceuticals. 2010; 3(4):1139-1161.
  14. ^ Oman T. J., Boettcher J. M., Wang H., Okalibe X. N., Van der Donk W. A (2011). "Sublancin is not a Lantibiotic but an s-Linked Glycopeptide". Nat Chem Biol. 7 (2): 78–80. doi:10.1038/nchembio.509. PMC 3060661 . PMID 21196935. 
  15. ^ Stepper J.; Shastri S.; Loo T. S.; Preston J. C.; Novak P.; Man P.; Moore C. H.; Havlíček V.; Patchett M. L.; Norris G. E (2011). "Cysteine s-Glycosylation, A New Post-Translational Modification Found In Glycopeptide Bacteriocins". FEBS Letters. 585: 645–650. doi:10.1016/j.febslet.2011.01.023. PMID 21251913. 
  16. ^ de Jong A; van Hijum S A F T; Bijlsma J J E; Kok J; Kuipers O P (2006). "BAGEL: a web-based bacteriocin genome mining tool". Nucleic Acids Research. 34: W273–W279. doi:10.1093/nar/gkl237. PMC 1538908 . PMID 16845009. 
  17. ^ Hammami R, Zouhir A, Ben Hamida J, Fliss I (2007). "BACTIBASE: a new web-accessible database for bacteriocin characterization". BMC Microbiology. 7: 89. doi:10.1186/1471-2180-7-89. PMC 2211298 . PMID 17941971. 
  18. ^ Hammami R, Zouhir A, Le Lay C, Ben Hamida J, Fliss I (2010). "BACTIBASE second release: a database and tool platform for bacteriocin characterization". BMC Microbiology. 10: 22. doi:10.1186/1471-2180-10-22. PMC 2824694 . PMID 20105292. 
  19. ^ Nardis, C.; Mastromarino, P.; Mosca, L. (Sep–Oct 2013). "Vaginal microbiota and viral sexually transmitted diseases". Annali di Igiene. 25 (5): 443–56. doi:10.7416/ai.2013.1946. PMID 24048183. 
  20. ^ Farkas-Himsley H, Yu H (1985). "Purified colicin as cytotoxic agent of neoplasia: comparative study with crude colicin". Cytobios. 42 (167–168): 193–207. PMID 3891240. 
  21. ^ Baumal R, Musclow E, Farkas-Himsley H, Marks A (1982). "Variants of an interspecies hybridoma with altered tumorigenicity and protective ability against mouse myeloma tumors". Cancer Res. 42 (5): 1904–8. PMID 7066902. 
  22. ^ Saito H, Watanabe T, Osasa S, Tado O (1979). "Susceptibility of normal and tumor cells to mycobacteriocin and mitomycin C". Hiroshima J. Med. Sci. 28 (3): 141–6. PMID 521305. 
  23. ^ Cruz-Chamorro L, Puertollano MA, Puertollano E, de Cienfuegos GA, de Pablo MA (2006). "In vitro biological activities of magainin alone or in combination with nisin". Peptides. 27 (6): 1201–9. doi:10.1016/j.peptides.2005.11.008. PMID 16356589. 
  24. ^ Sand SL, Haug TM, Nissen-Meyer J, Sand O (2007). "The bacterial peptide pheromone plantaricin A permeabilizes cancerous, but not normal, rat pituitary cells and differentiates between the outer and inner membrane leaflet". J. Membr. Biol. 216 (2–3): 61–71. doi:10.1007/s00232-007-9030-3. PMID 17639368. 
  25. ^ Farkas-Himsley H, Hill R, Rosen B, Arab S, Lingwood CA (1995). "The bacterial colicin active against tumor cells in vitro and in vivo is verotoxin 1". Proceedings of the National Academy of Sciences of the United States of America. 92 (15): 6996–7000. doi:10.1073/pnas.92.15.6996. PMC 41458 . PMID 7624357. 
  26. ^ Musclow CE, Farkas-Himsley H, Weitzman SS, Herridge M (1987). "Acute lymphoblastic leukemia of childhood monitored by bacteriocin and flowcytometry". Eur J Cancer Clin Oncol. 23 (4): 411–8. doi:10.1016/0277-5379(87)90379-8. PMID 3475205. 
  27. ^ Farkas-Himsley H, Zhang YS, Yuan M, Musclow CE (1992). "Partially purified bacteriocin kills malignant cells by apoptosis: programmed cell death". Cell. Mol. Biol. (Noisy-le-grand). 38 (5–6): 643–51. PMID 1483114. 
  28. ^ Farkas-Himsley H, Musclow CE (1986). "Bacteriocin receptors on malignant mammalian cells: are they transferrin receptors?". Cell. Mol. Biol. 32 (5): 607–17. PMID 3779762. 
  29. ^ Farkas-Himsley H, Freedman J, Read SE, Asad S, Kardish M (1991). "Bacterial proteins cytotoxic to HIV-1-infected cells". AIDS. 5 (7): 905–7. doi:10.1097/00002030-199107000-00025. PMID 1892605. Could someone please quote the relevant text 
  30. ^ "What Comes After Antibiotics? 5 Alternatives to Stop Superbugs". Popular Mechanics. Retrieved 2013-12-21. 
  31. ^ Fahim, Hazem A.; Khairalla, Ahmed S.; El-Gendy, Ahmed O. (2016-01-01). "Nanotechnology: A Valuable Strategy to Improve Bacteriocin Formulations". Food Microbiology. 7: 1385. doi:10.3389/fmicb.2016.01385. 
  32. ^ Naclerio, G; Ricca, E; Sacco, M; De Felice, M (December 1993). "Antimicrobial activity of a newly identified bacteriocin of Bacillus cereus". Appl Environ Microbiol. 59 (12): 4313–6. PMC 195902 . PMID 8285719. 
  33. ^ Kawai Y, Kemperman R, Kok J, Saito T (2004). "The circular bacteriocins gassericin A and circularin A". Current Protein & Peptide Science. 5 (5): 393–8. doi:10.2174/1389203043379549. PMID 15544534. Retrieved 2015-01-19. 
  34. ^ Pandey N, Malik RK, Kaushik JK, Singroha G (2013). "Gassericin A: a circular bacteriocin produced by lactic acid bacteria Lactobacillus gasseri". World Journal of Microbiology & Biotechnology. 29 (11): 1977–87. doi:10.1007/s11274-013-1368-3. PMID 23712477. 
  35. ^ Mørtvedt, C. I.; Nissen-Meyer, J.; Sletten, K.; Nes, I. F. (1991). "Purification and amino acid sequence of lactocin S, a bacteriocin produced by Lactobacillus sake L45". Applied and Environmental Microbiology. 57 (6): 1829–1834. PMC 183476 . PMID 1872611. 
  36. ^ Bogaardt, C.; van Tonder, A. J.; Brueggemann, A. (2015). "Genomic analyses of pneumococci reveal a wide diversity of bacteriocins – including pneumocyclicin, a novel circular bacteriocin". BMC Genomics. 16: 554. doi:10.1186/s12864-015-1729-4. PMC 4517551 . PMID 26215050. 
  37. ^ Michel-Briand, Y.; Baysse, C. (2002). "The pyocins of Pseudomonas aeruginosa". Biochimie. 84 (5–6): 499–510. doi:10.1016/s0300-9084(02)01422-0. PMID 12423794. 
  38. ^ Kabuki T, Saito T, Kawai Y, Uemura J, Itoh T (1997). "Production, purification and characterization of reutericin 6, a bacteriocin with lytic activity produced by Lactobacillus reuteri LA6". International Journal of Food Microbiology. 34 (2): 145–56. doi:10.1016/s0168-1605(96)01180-4. PMID 9039561. Retrieved 2015-01-19. 
  39. ^ Wescombe, PA; Upton, M; Dierksen, KP; Ragland, NL; Sivabalan, S; Wirawan, RE; Inglis, MA; Moore, CJ; Walker, GV; Chilcott, CN; Jenkinson, HF; Tagg, JR (February 2006). "Production of the lantibiotic salivaricin A and its variants by oral streptococci and use of a specific induction assay to detect their presence in human saliva". Applied and Environmental Microbiology. 72 (2): 1459–66. doi:10.1128/aem.72.2.1459-1466.2006. PMC 1392966 . PMID 16461700. 
  40. ^ Müller, Ina; Lurz, Rudi; Geider, Klaus (25 July 2012). "Tasmancin and lysogenic bacteriophages induced from Erwinia tasmaniensis strains". Microbiological Research. 167 (7): 381–387. doi:10.1016/j.micres.2012.01.005. 

External linksEdit