Snowy Owl
Retired in 2010, In Memoriam
Antimicrobial Peptides
Posted by ajcann on May 7th, 2007
We are entering the Post-Antibiotic Era, a time when antibiotics are losing their almost magical effectiveness as bacteria become resistant to clinically useful drugs.
Medicine is in desperate need of alternative therapies for infectious diseases.
Naturally-occurring antimicrobial compounds offer potentially very attractive prospects in these times.
Peptides (short chains of amino acids) with antimicrobial activities are part of the innate immunity of almost all living organisms, protecting them from infection and competition.
This includes bacteria, plants and animals all the way up to mammals.
As a result, an enormous diversity of antimicrobial peptides exists, both in terms of both structure and in activity.
Individual peptides may be active against bacteria, viruses, fungi or other types of microorganism.
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Typical antimicrobial peptides are between 12 and 50 amino acids in length. Although they are very diverse in structure, most include two or more positively charged residues such as arginine, lysine or histidine, and usually over 50% hydrophobic amino acids.
These peptides exert their antimicrobial effects in a variety of ways, including membrane permeabilization and by interfering with metabolism by targeting many different cytoplasmic components.
In many cases, the antimicrobial activity has been identified by bioassay, and the exact mechanism of killing is not known.
In addition to killing microorganisms directly, such peptides may also interact with the immune system. Although this is undoubtedly a valuable biological property, from the point of view of replacing antibiotics, directly bacteriocidal peptides are the most interesting type.
One of the most exciting things about antimicrobial peptides is that in contrast to conventional antibiotics, they generally have a broad range of activity, but do not appear to induce resistance. Part of the reason for this is that they are mostly bacteriocidal as opposed to bacteriostatic and require a short contact time to induce killing. In other words, organisms which encounter effective concentrations of these compounds are usually killed before resistance has time to develop.
Consequently, there has been much interest in searching for these agents in recent years. ANTIMIC, an online database of antimicrobial sequences contains nearly 2000 peptide sequences known to have some sort of antimicrobial activity (Nucleic Acids Res 2004 32: D586-9). A considerable number of peptides are currently being investigated in clinical trials, although none have yet found their way into widespread use.
Along with many lower animals, amphibian skin is one of the most generous sources of these peptides. Several novel molecules have been discovered and these serve to protect amphibians, living in a soup of potential pathogens, from infection (Antimicrobial peptides from amphibian skin: an expanding scenario. Curr Opin Chem Biol. 2002 6: 799-804).
An example of this is a recent report of ranalexin, a 20-residue antimicrobial peptide isolated from the skin of the American bullfrog Rana catesbeiana, as a treatment for the antibiotic resistant ?superbug? MRSA. Of course, in addition to using naturally occurring peptides directly as drugs, they can also serve as templates for the design of novel synthetic antimicrobial compounds.
As these are quite potent molecules, they usually occur in only vanishingly small quantities in their natural hosts. Consequently, it is usually difficult to purify enough of the peptide even for analysis, let alone for widespread clinical use. As the clinical potential of these peptides becomes more obvious, attention is turning to better production methods such as heterologous microbial expression systems, which allow the compounds to be produced in useful quantities by convenient organisms such as Escherichia coli (Recombinant production of antimicrobial peptides in heterologous microbial systems. Biotechnol Appl Biochem. 2007 47: 1-9).
Hopefully these naturally occurring compounds and artificial derivatives based on them will be able to assist in the fight against the rise of the antibiotic resistant superbugs.
Posted by ajcann on May 7th, 2007
We are entering the Post-Antibiotic Era, a time when antibiotics are losing their almost magical effectiveness as bacteria become resistant to clinically useful drugs.
Medicine is in desperate need of alternative therapies for infectious diseases.
Naturally-occurring antimicrobial compounds offer potentially very attractive prospects in these times.
Peptides (short chains of amino acids) with antimicrobial activities are part of the innate immunity of almost all living organisms, protecting them from infection and competition.
This includes bacteria, plants and animals all the way up to mammals.
As a result, an enormous diversity of antimicrobial peptides exists, both in terms of both structure and in activity.
Individual peptides may be active against bacteria, viruses, fungi or other types of microorganism.
Subscribe to podcasts (free):
[iTunes] Enhanced podcasts
[RSS] mp3 podcasts (audio only)
Play this episode: Enhanced version
Audio only:
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Typical antimicrobial peptides are between 12 and 50 amino acids in length. Although they are very diverse in structure, most include two or more positively charged residues such as arginine, lysine or histidine, and usually over 50% hydrophobic amino acids.
These peptides exert their antimicrobial effects in a variety of ways, including membrane permeabilization and by interfering with metabolism by targeting many different cytoplasmic components.
In many cases, the antimicrobial activity has been identified by bioassay, and the exact mechanism of killing is not known.
In addition to killing microorganisms directly, such peptides may also interact with the immune system. Although this is undoubtedly a valuable biological property, from the point of view of replacing antibiotics, directly bacteriocidal peptides are the most interesting type.
One of the most exciting things about antimicrobial peptides is that in contrast to conventional antibiotics, they generally have a broad range of activity, but do not appear to induce resistance. Part of the reason for this is that they are mostly bacteriocidal as opposed to bacteriostatic and require a short contact time to induce killing. In other words, organisms which encounter effective concentrations of these compounds are usually killed before resistance has time to develop.
Consequently, there has been much interest in searching for these agents in recent years. ANTIMIC, an online database of antimicrobial sequences contains nearly 2000 peptide sequences known to have some sort of antimicrobial activity (Nucleic Acids Res 2004 32: D586-9). A considerable number of peptides are currently being investigated in clinical trials, although none have yet found their way into widespread use.
Along with many lower animals, amphibian skin is one of the most generous sources of these peptides. Several novel molecules have been discovered and these serve to protect amphibians, living in a soup of potential pathogens, from infection (Antimicrobial peptides from amphibian skin: an expanding scenario. Curr Opin Chem Biol. 2002 6: 799-804).
An example of this is a recent report of ranalexin, a 20-residue antimicrobial peptide isolated from the skin of the American bullfrog Rana catesbeiana, as a treatment for the antibiotic resistant ?superbug? MRSA. Of course, in addition to using naturally occurring peptides directly as drugs, they can also serve as templates for the design of novel synthetic antimicrobial compounds.
As these are quite potent molecules, they usually occur in only vanishingly small quantities in their natural hosts. Consequently, it is usually difficult to purify enough of the peptide even for analysis, let alone for widespread clinical use. As the clinical potential of these peptides becomes more obvious, attention is turning to better production methods such as heterologous microbial expression systems, which allow the compounds to be produced in useful quantities by convenient organisms such as Escherichia coli (Recombinant production of antimicrobial peptides in heterologous microbial systems. Biotechnol Appl Biochem. 2007 47: 1-9).
Hopefully these naturally occurring compounds and artificial derivatives based on them will be able to assist in the fight against the rise of the antibiotic resistant superbugs.