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DATABASES |
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| INTRODUCTION |
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Molecules isolated from bacteria that have demonstrated bactericidal activity are called bacteriocins. Ribosomally synthesized peptide bacteriocins from Gram-positive bacteria can be subdivided into two major classes. Bacteriocins of class I are characterized by having modified amino acid residues (e.g, lantibiotics) and bacteriocins of class II are characterized by not possessing modified amino acid residues (e.g, small heat stable non-lantibiotics).
These two classes are the most studied due to their abundance and their potential use for industrial applications. They are similar in size (approx 20-60 amino acids), mostly cationic, and possess a hydrophobic domain and/or amphiphilic region, which may relate to their activity on membranes. The defining characteristic of lantibiotics is that they contain the unusual amino acids lanthionine or Β-methyllanthionine.
Generally, type A lantibiotics are characterized by being strongly cationic (with 2 to 7 net positive charge), having molecular masses more than 2100 Da, and having rigid ring conformations separated by areas of flexibility.
It is currently believed that their primary bactericidal activity is mediated through the formation of voltage-dependent membrane channels. By contrast, type B lantibiotics are characterized by being neutral or slightly anionic with a 0 to –1 net charge, having molecular masses of less than 2100 Da, and having a more compact globular structure. Their primary function is mediated through the inhibition of essential enzymes. There is a unique group of lantibiotics called the two-peptide bacteriocins. In this system, two genes encoding each of the peptides are located next to each other and both of the peptides are required for bactericidal activity. Each peptide is either inactive or only slightly active when tested individually. The mode of bactericidal activity is believed to be the same as for type A lantibiotics. In some cases, they have been grouped along with type A lantibiotics.
Lantibiotics are produced by a large number of Gram positive bacteria such as Streptococcus and Streptomyces to attack other gram positive bacteria and as such they are considered a member of the bacteriocins.
Lantibiotics are well studied because of the commercial use of these bacteria in the food industry for making dairy products such as cheese. Bacteriocins are classified according to their extent of posttranslational modification. The lantibiotics are a class of more extensively modified bacteriocins, also called Class I. Bacteriocins for which disulfide bonds are the only modification to the peptide are Class II bacteriocins. Most bacteriocins are biologically active single-chain peptides. Some are only active as partners with a second peptide.
Nisin and epidermin are members of a family of lantibiotics that bind to a cell wall precursor lipid component of target bacteria and disrupt cell wall production. The duramycin family of lantibiotics binds phosphoethanolamine in the membranes of its target cells and seem to disrupt several physiological functions.
The name Lantibiotics was introduced in 1988 as an abbreviation for "Lanthionine-containing peptide antibiotics". In spite of this naming, Lantibiotics are not classed as antibiotics. One reason for this is that they are constructed ribosomally while antibiotics are constructed by enzyme action. The first structures of these antimicrobial agents were produced by pioneering work by Gross and Morell in the late sixties and early seventies, thus marking the formal introduction of Lantibiotics. Since then Lantibiotics such as Nisin have been used auspiciously for food preservation and have yet to encounter significant bacterial resistance. These attributes of lantibiotics have led to more detailed research into their structures and biosynthetic pathways.
Type A Lantibiotics are long flexible molecules- eg Nisin, subtilin, epidermin. Subgroup AI includes Mutacin II, subgroup AII includes Mutacin I & III. Type B Lantibiotics are globular- eg mersacidin, actagardine, cinnamycin.
The biosynthesis is interesting. They are synthesised with a leader polypeptide sequence which is only removed during the transport of the molecule out of the synthesising cell. They are synthesized by ribosomes, which distinguishes them from antibiotics which are synthesized by enzymes.
Lantibiotics show substantial specificity for some components (eg lipid II) of bacterial cell membranes especially of Gram positive bacteria. Type A kill rapidly by pore formation, type B inhibit peptidoglycan biosynthesis. See Brotz & Sahl for discussion of mechanism of action. They are active in very low concentrations.
Lantibiotics are produced by Gram-positive bacteria and show strong antimicrobial action towards a wide range of other Gram-positive bacteria. As such they have become attractive candidates for use in food preservation (by inhibiting pathogens that cause food spoilage) and the pharmaceutical industry (to prevent or fight infections in humans or animals). See C. van Kraaij et al., Nat. Prod. Rep. (1999), 16, 583-584 for more detailed discussion of the pharmaceutical application of lantibiotics.
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| SLIDE SHOW |
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