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[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.
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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.
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]
The class I bacteriocins are small peptide inhibitors and include nisin and other lantibiotics.
The class II bacteriocins are small (<10 kDa)heat-stable proteins. This class is subdivided into five subclassses. 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. One exaple of Class IIa bacteriocin is pediocin PA-1[7]. 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 ions such as Na and K, but not for divalents ones. Class IIc encompasses ciclic peptides, which possesses the N-teminal and C-terminal regions covalentely linked. Enterocin AS-48 is the prototype of this group. Class IId cover single-peptide bacteriocins, which are not post-translated modified and do not show the pediocin-like signature. The beste example of this group is the highly stable aureocin A53. This bacteriocin is stable under highly acidic environment (HCl 6 N), not affected by proteases and thermoresistant [8]. The most recently proposed subclass is the Class IIe, which encompasses those bacteriocins composed by three or four non-pediocin like peptides. The best exemple is aureocin A70, a four-peptides bacteriocin, highly active agains L. monocytogenes, with a enormous biotechnological application [9].
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 several Staphylococcus spp. cell walls, principally S. aureus[10]. Subclass IIIb, in contrast, comprises those peptides that do not cause cell lysis, killing the target cells by disrupting the membrane potencial, which causes ATP efflux .
Two databases of bacteriocins are available: BAGEL[11] and BACTIBASE.[12][13]
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.[14][15] They have shown distinct promise as a diagnostic agent for some cancers,[16][17][18][19][20] 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.[21][22]
Bacteriocins (which?) were tested as AIDS drugs (around 1990) [23] but not progressed beyond in-vitro tests on cell lines.
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.
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