Antimicrobial peptides

Antimicrobial peptides (AMPs) are small peptides (~4-15 kDa) that kill microbes, fungi, protozoa, while possessing the ability to inactivate viruses.  These peptides do not exert their effects in an enzymatic (catalytic) manner, but in a dose-dependent manner. There are more than 1,000 families of antimicrobial peptides that have been identified in the animal kingdom.  These peptides are generally small in size (6 -100 amino acids), often positively charged (cationic) and amphipathic (possess both hydrophobic and hydrophilic regions). AMPs adopt different secondary structures, which is used to classify them into different molecular families (Peters et al, 2010). The structural classes include  β-sheet, α-helical, loop, and extended peptides.  The molecules may also be stabilised by disulphide bonds.

More than 800 different AMPs have been identified to date and it is thought that all multicellular organisms are capable to synthesising AMPs.

The mechanism of action of AMPs is not clear.  Three distinct models have been proposed: the barrel-stave pore model, the thoroidal pore model, or the carpet model (Palffy et al, 2009), although a number of variations of these models have also been described. In essence, AMPs disrupt microbial cell membranes, causing proteins channels to be formed within those membranes.  This causes the cells' cytoplasmic contents to leak out of those cells, resulting in their deaths.  It is not clear how AMPs distinguish between microbial membranes and host cell membranes.  AMPs specifically exert their effects on microbial cell membranes.  It is thought that amps exploit differences in the architectures of microbial and eukaryotic cell membranes.  However, this does not explain the ability of AMPs to destroy protozoan and fungal cells, without causing damage to host cells. 

Unlike antibiotic resistance, resistance to amps is rare in nature.  Indeed, scientists believe that amps may provide an avenue for treating infections by antibiotic-resistant microbes.  


Classes of antimicrobial peptides: This figure shows the four major classes of antimicrobial peptides.  Antimicrobial peptides are classified on the basis of their structures. Figure is from Peters et al (2010).


Modes of action: The interaction of AMPs with microbial cell membranes:  (A) Barrel-stave pore model; (B) thoroidal pore model; (C) carpet model. The AMPs cause channels to form within the membranes, causing cytoplasmic content to leak out of microbial cells.  Figure is from Palffy et. al. (2009).

References

Peters BM, Shirtliff ME, Jabra-Rizk MA (2010) Antimicrobial Peptides: Primeval Molecules or Future Drugs? PLoS Pathog 6(10): e1001067.

Image credits

Pálffy, R., Gardlík, R., Behuliak, M., Kadasi, L., Turna, J and Celec, P. On the Physiology and Pathophysiology of Antimicrobial Peptides. Mol Med. 2009. 15:51–59.


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© Sham Nair 2014