Bacteriocin

Bacteriocins are proteinaceous toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are typically considered to be narrow spectrum antibiotics, though this has been debated.^[1] They are phenomenologically analogous to yeast and paramecium killing factors, and are structurally, functionally, and ecologically diverse.

Bacteriocins were first discovered by A. Gratia in 1925. A Gratia was given the credit for the discovery but many scientists such as Christopher Sobieralski believe that Bacteriocins were actually discovered in a microcosm living on Garrets fingernails^[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 bacteriocins

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. For example the bacteriocins produced by Staphylococcus warneri are called as warnerin^[5] or warnericin. 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.

Methods of classification

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

One method of classification fits the bacteriocins into Class I, Class IIa/b/c, and Class III. ^[6]

Class I bacteriocins

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

Class II bacteriocins

The class II bacteriocins are small heat-stable proteins. 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 antilisterial activity, and broad range of activity. The class IIb bacteriocins (two-peptide bacteriocins) require two different peptides for activity. Other bacteriocins can be grouped together as Class IIc (circular bacteriocins). These have a wide range of effects on membrane permeability, cell wall formation and pheromone actions of target cells.

Class III bacteriocins

Class III bacteriocins are large, heat-labile protein bacteriocins.

Databases

Two databases of bacteriocins are available: BAGEL^[7] and BACTIBASE.^[8][9]

Medical significance

Bacteriocins are of interest in medicine because they are made by non-pathogenic bacteria that normally colonize the human body. Loss of these harmless bacteria following antibiotic use may allow opportunistic pathogenic bacteria to invade the human body.

Bacteriocins have also been suggested as a cancer treatment.^[10][11] They have shown distinct promise as a diagnostic agent for some cancers,^{[12][13][14][15][16]} but their status as a form of therapy remains experimental and outside the main thread of cancer research. Partly this is 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.^[17][18]

Bacteriocins (which?) were tested as AIDS drugs (around 1990) ^[19] but not progressed beyond in-vitro tests on cell lines.

Production

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 name

• acidocin
• actagardine
• agrocin
• alveicin
• aureocin
• carnocin
• carnocyclin
• colicin
• curvaticin
• divercin
• duramycin
• enterocin
• enterolysin
• epidermin/gallidermin
• erwiniocin
• glycinecin
• halocin
• haloduracin
• lactococin
• lacticin
• leucoccin
• macedocin
• mersacidin
• mesentericin
• microbisporicin
• mutacin
• nisin
• paenibacillin
• planosporicin
• pediocin
• pentocin
• plantaricin
• reutericin
• sakacin
• salivaricin
• subtilin
• sulfolobicin
• thuricin 17
• trifolitoxin
• variacin
• vibriocin
• warnericin
• warnerin

See also

• Peripheral membrane proteins

References

1. ^ Farkas-Himsley H (1980). "Bacteriocins--are they broad-spectrum antibiotics?". J. Antimicrob. Chemother. 6 (4): 424–6. doi:10.1093/jac/6.4.424. PMID 7430010. 
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. http://www.genetics.org/cgi/pmidlookup?view=long&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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847374. 
5. ^ Prema P, Bharathy S, Palavesam A, Sivasubramanian M, Immanuel G (2006). "Detection, purification and efficacy of warnerin produced by Staphylococcus warneri". World Journal of Microbiology and Biotechnology 22 (8): 865–72. doi:10.1007/s11274-005-9116-y. 
6. ^ 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. http://www.nature.com/nrmicro/journal/v4/n2/full/nrmicro1273-c2.html.  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. http://www.nature.com/nrmicro/journal/v4/n2/full/nrmicro1273-c2.html. 
7. ^ 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 (9): W273–W279. doi:10.1093/nar/gkl237. PMID 1538908. 
8. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2211298. 
9. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2824694. 
10. ^ 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. 
11. ^ 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. 
12. ^ 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. 
13. ^ 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. 
14. ^ 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. 
15. ^ 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". Proc. Natl. Acad. Sci. U.S.A. 92 (15): 6996–7000. doi:10.1073/pnas.92.15.6996. PMC 41458. PMID 7624357. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=41458. 
16. ^ 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. 
17. ^ 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. 
18. ^ 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. 
19. ^ 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" 

External links

• Bagel Bacteriocin Database
• BACTIBASE Database

External links

• MeSH Bacteriocins