Antimicrobial peptides

Antimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum of antimicrobial activity against bacteria, viruses, and fungi (Zasloff M 2002; Radek K & Gallo R 2007). The majority of known AMPs are cationic peptides with common structural characteristics where domains of hydrophobic and cationic amino acids are spatially arranged into an amphipathic design, which facilitates their interaction with bacterial membranes (Shai Y 2002; Yeaman MR & Yount NY 2003; Brown KL & Hancock RE 2006; Dennison SR et al. 2005; Zelezetsky I & Tossi A 2006). It is generally excepted that the electrostatic interaction facilitates the initial binding of the positively charged peptides to the negatively charged bacterial membrane. Moreover, the structural amphiphilicity of AMPs is thought to promote their integration into lipid bilayers of pathogenic cells, leading to membrane disintegration and finally to the microbial cell death. In addition to cationic AMPs a few anionic antimicrobial peptides have been found in humans, however their mechanism of action remains to be clarified (Lai Y et al. 2007; Harris F et al. 2009; Paulmann M et al. 2012). Besides the direct neutralizing effects on bacteria AMPs may modulate cells of the adaptive immunity (neutrophils, T-cells, macrophages) to control inflammation and/or to increase bacterial clearance.

AMPs have also been referred to as cationic host defense peptides, anionic antimicrobial peptides/proteins, cationic amphipathic peptides, cationic AMPs, host defense peptides and alpha-helical antimicrobial peptides (Brown KL & Hancock RE 2006; Harris F et al. 2009; Groenink J et al. 1999; Bradshaw J 2003; Riedl S et al. 2011; Huang Y et al. 2010).

The Reactome module describes the interaction events of various types of human AMPs, such as cathelicidin, histatins and neutrophil serine proteases, with conserved patterns of microbial membranes at the host-pathogen interface. The module includes also proteolytic processing events for dermcidin (DCD) and cathelicidin (CAMP) that become functional upon cleavage. In addition, the module highlights an AMP-associated ability of the host to control metal quota at inflammation sites to influence host-pathogen interactions.