Bacteriocins
Microorganisms produce an extraordinary array of defence systems. These include classical antibiotics, metabolic by-products such as the production of lactic acids by lactobacilli, lytic agents such as lysozymes, protein exotoxins and bacteriocins. Bacteriocins are found in almost every bacterial species, and in some species, tens or even hundreds of different kinds of bacteriocin are produced (Bacteriocins: Evolution, Ecology, and Application. 2002 Annual Review of Microbiology 56: 117-137). Much of the diversity of bacteriocins has been shown to be produced by domain shuffling during recombination of related genes from different species.
These compounds are frequently named after the bacteria which produce them, e.g. halobacteria produce halocins, Streptomycetes commonly produce broad-spectrum antibiotics such as streptomycin and Escherichia coli produces colicins. Bacteriocins differ from traditional antibiotics in one major way: they have a relatively narrow killing spectrum and are only toxic to bacteria which are closely related to the producing strain. The bacteria invest considerable amounts of valuable energy in the production of these antimicrobial compounds, so it is clear that they must have a positive benefit for the organisms. With the rise of more and more multi-antibiotic resistant pathogens, attention is turning to the potential application of these toxins in human health, but also in agriculture and the growing use of bacteriocins in food preservation.
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Among Gram-negative bacteria, the colicins produced by Escherichia coli have been more intensively studied than any other type. Colicin gene clusters are composed of a colicin gene, which encodes the toxin; an immunity gene, which encodes a protein conferring specific immunity to the producer cell by binding to and inactivating the toxin protein and a lysis gene, which encodes a protein involved in colicin release through lysis of the producer cell. These gene clusters are encoded on plasmids in E. coli. Colicin production is controlled by the SOS system and they are therefore principally produced under times of stress. The killing mechanisms of colicins range from pore formation in the cell membrane to nuclease activity against DNA and RNA targets. Like all of the bacteriocins produced by Gram-negative bacteria, colicins are relatively large proteins, but they vary considerably in size from 178 to 777 amino acids.
Bacteriocins produced by Gram-positive bacteria are even more diverse than those found in Gram-negative species. Bacteriocin production by Gram-positive species is not necessarily the lethal event it usually is for Gram-negative bacteria. This is due to transport mechanisms in Gram-positive bacteria which efficiently export the bacteriocins from the producer cell (as opposed to requiring lysis of the producer for release). The Archaea also produce their own distinct family of bacteriocin-like antimicrobials, known as archaeocins. The only well-characterized proteins of this type are the halocin family produced by Halobacterium.
The rise and spread of multi-resistant bacterial pathogens has forced us to consider alternative methods of combating infections. One of the limitations of using broad-spectrum antibiotics is that they kill almost any bacterial species which is not resistant to the drug. This upset of the normal body flora can cause problems, but also results in intensive selection pressure for the evolution of antibiotic resistance in both pathogens and commensal bacteria. Once antibiotic resistance appears, it is simply a matter of time and the intensity of selection before human pathogens acquire resistance. Bacteriocins can be considered “designer drugs” with a relatively narrow spectrum of killing activity, targeted against specific bacterial pathogens. Given the diversity of bacteriocins produced in nature, it is a relatively simple task to find bacteriocins active against specific human pathogens.
Although the clinical applications of these proteins are still in the future, one area where bacteriocins have been put to practical use is in food preservation. The only bacteriocins currently used for food preservation are those produced by lactic acid bacteria and these are used in the production of fermented foods. Because lactic acid bacteria have been used for centuries to ferment foods, they enjoy GRAS (generally regarded as safe) status by the U.S. Food and Drug Administration (FDA). Nisin was the first bacteriocin to be isolated and approved for use in foods, specifically to prevent the growth of Clostridium botulinum in cheese spreads. Nisin is currently accepted as a safe food preservative by over 45 countries.
Plant disease control relies mainly on chemical pesticides which are subject to strong restrictions and regulatory requirements. Antimicrobial peptides are also interesting compounds for plant health and several have been used as the basis for the design of new synthetic analogues, which are expressed in transgenic plants to confer disease protection or secreted by microorganisms which are active ingredients of commercial biopesticides (Antimicrobial peptides and plant disease control. FEMS Microbiol Lett. 2007 270: 1-11).
Although bacteriocins have been studied for quite a long time, we have a hazy understanding of the diverse roles these toxins play in mediating microbial dynamics and maintaining microbial diversity. The impact of such studies is not solely academic. The potential for bacteriocins to serve as alternatives to classical antibiotics in treating bacterial infections is real, and the application of bacteriocins in food preservation and in agriculture is expanding rapidly. The future roles bacteriocins may serve is limited only by our imagination.
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Tags: Agriculture, Antibiotics, Bacteria, Biology, Biotechnology, Genetics, Health, Medicine, Microbiology, Podcast, Science
I’ve read that CA-MRSA produces an enzyme that kills neutrophils. Has S. aureus always had this property or is this a result of a mutation from the antibiotic resistance? And if it is, how are antibiotics creating such mutations?
No, the neutrophil killing ability of S. aureus is not related to antibiotic resistance.
Is this found more or less in all S.aureus strains or just the antibiotic resistant ones?
As far as I’m aware, all strains of S. aureus produce bacteriocins (not all the same, but this is unrelated to antibiotic resistance.