Antimicrobial peptides (also called host defence peptides) are an evolutionarily conserved component of the innate immune response and are found among all classes of life.

These peptides are potent, broad spectrum antibiotics which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram negative and Gram positive bacteria (including strains that are resistant to conventional antibiotics), mycobacteria (including Mycobacterium tuberculosis), enveloped viruses, fungi and even transformed or cancerous cells. Unlike the majority of conventional antibiotics it appears as though antimicrobial peptides may also have the ability to enhance immunity by functioning as immunomodulators. An antibiotic is a drug that kills or slows the growth of bacteria. ... Gram-negative bacteria are those that do not retain crystal violet dye in the Gram staining protocol. ... Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to Gram-negative bacteria, which are not affected by the stain. ... Species See text. ... Binomial name Mycobacterium tuberculosis Zopf 1883 Mycobacterium tuberculosis is the bacterium that causes most cases of tuberculosis[1]. It was first described on March 24, 1882 by Robert Koch, who subsequently received the Nobel Prize in physiology or medicine for this discovery in 1905. ...

Structure

Antimicrobial peptides are short proteins, generally between 12 and 50 amino acids long (although larger proteins with similar properties such as lysozyme are often classified as antimicrobial peptides). These peptides include two or more positively charged residues provided by arginine, lysine or, in acidic environments, histidine, and a large proportion (generally >50%) of hydrophobic residues.^[1][2] The secondary structures of these molecules follow 4 themes, including i) α-helical, ii) β-stranded due to the presence of 2 or more disulphide bonds, iii) β-hairpin or loop due to the presence of a single disulphide bond and/or cyclization of the peptide chain, and iv) extended. Many of these peptides are unstructured in free solution, and fold into their final configuration upon partitioning into biological membranes. The ability to associate with membranes is a definitive feature of antimicrobial peptides ^[3] although membrane permeabilisation is not necessarily the even though the peptides have a variety of antimicrobial activities ranging from membrane permeabilization to action on a range of cytoplasmic targets. A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... The general structure of an amino acid molecule, with the amine group on the left and the carboxyl group on the right. ... Lysozyme 3D structure. ... Arginine (symbol Arg or R) is an α-amino acid. ... Lysine is one of the 20 amino acids normally found in proteins. ... Histidine is one of the 20 most common natural amino acids, coded for in DNA. Nutritionally, in humans, histidine is considered an essential amino acid, but mostly only in children. ... A diagram of the alpha helix structure of amino acids In proteins, the α helix is a major structural motif in secondary structure. ... Diagram of Î’-Pleated sheet and bond structure of protein The β sheet (also β-pleated sheet) is a commonly occurring form of regular secondary structure in proteins, first proposed by Linus Pauling and Robert Corey in 1951. ... A disulfide bond (SS-bond), also called a disulfide bridge, is a strong covalent bond between two sulfhydryl groups. ...

Antimicrobial Activities

The modes of action by which antimicrobial peptides kill bacteria is varied and includes disrupting membranes, interfering with metabolism, and targeting cytoplasmic components. In many cases the exact mechanism of killing is not known. In contrast to many conventional antibiotics these peptides appear to be bacteriocidal instead of bacteriostatic. In general the antimicrobial activity of these peptides is determined by measuring the minimal inhibitory concentration (MIC), which is the lowest concentration of drug that reduces growth by more than 50%.^[4] Bacteriocidal prevents and combats bacterial infection. ... Bacteriostatic antibiotics hamper the growth of bacteria by interfering with bacteria protein production, interfering with bacteria DNA production interfering with bacteria cellular metabolism Bacteriostatic antibiotics inhibit growth and repoduction of the bacteria, though do not kill it, while bactericidal antibiotics kill bacteria. ...

Immunomodulatory Activities

In addition to killing bacteria directly they have been demonstrated to have a number of immunomodulatory functions that may be involved in the clearance of infection, including the ability to alter host gene expression, act as chemokines and/or induce chemokine production, inhibiting lipopolysaccharide induced pro-inflammatory cytokine production, promoting wound healing, and modulating the responses of dendritic cells and cells of the adaptive immune response. Animal models indicate that host defence peptides are crucial for both prevention and clearance of infection. It appears as though many peptides initially isolated as and termed “antimicrobial peptides” have been shown to have more significant alternative functions in vivo (e.g. hepcidin ^[5]). Chemokines are a family of pro-inflammatory activation-inducible cytokines, or small protein signals secreted by cells. ... It has been suggested that this article or section be merged with endotoxin. ... Cytokines is a group of proteinaceous signalling compounds that like hormones and neurotransmitters are used extensively for inter-cell communication. ... Dendritic cells (DC) are immune cells and form part of the mammal immune system. ...

Therapeutic Potential

These peptides are excellent candidates for development as novel therapeutic agents and complements to conventional antibiotic therapy because in contrast to conventional antibiotics they do not appear to induce antibiotic resistance while they generally have a broad range of activity, are bacteriocidal as opposed to bacteriostatic and require a short contact time to induce killing. A number of naturally occurring peptides and their derivatives have been developed as novel anti-infective therapies for conditions as diverse as oral mucositis, lung infections associated with cystic fibrosis (CF) and topical skin infections.

Notes and references

1. ↑  Papagianni, M. 2003. Ribosomally synthesized peptides with antimicrobial properties: biosynthesis, structure, function, and applications. Biotechnol Adv 21:465.
2. ↑  Sitaram, N., and R. Nagaraj. 2002. Host-defense antimicrobial peptides: importance of structure for activity. Curr Pharm Des 8:727.
3. ↑  Hancock, R. E. W., and A. Rozek. 2002. Role of membranes in the activities of antimicrobial cationic peptides. FEMS Microbiol Lett 206:143.
4. ↑  National Committee of Laboratory Safety and Standards (NCLSS) as published in Amsterdam, D. 1996. Susceptibility testing of Antimicrobials in liquid media. In "Antibiotics in Laboratory Medicine", Lorian, V., ed. Fourth Edition, pp.52-111. Williams and Wilkins, Baltimore
5. ↑  Hunter, H. N., D. B. Fulton, T. Ganz, and H. J. Vogel. 2002. The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. J Biol Chem 277:37597.

External links

• A good basic overview of cationic peptides.