Cationic host defense peptides

Figure 5 Direct antimicrobial and immunomodulatory activities of host defense peptides. Cationic host defense peptides exert their anti-infective activities through either direct antimicrobial activity or through modulation of the host immune response. HDP-mediated direct antimicrobial activity has been demonstrated in vivo for those HDPs that are either present at physiological concentrations that match their respective MIC values or are not inhibited by high salt or divalent cation concentrations. Most natural HDPs have also been demonstrated to be involved in the induction of innate and adaptive immune responses within the host as well as the selective suppression of proinflammatory responses. Ultimately,...

It has also been demonstrated that the transmembrane potentials of prokaryotes are typically 50% greater than their eukaryotic counterparts. This chemiosmotic potential has been proposed to act electrophoretically on host defense peptides attached to the microbial surface. It should also be noted that although increased cationicity of the host defense peptides is generally associated with increased antimicrobial activity there is a threshold by which selectivity between host and microbial cells is lost at the behest of increased cationicity. 

Structure-activity relationship studies investigating the antimicrobial activities of host defense peptides have primarily sought the characterization of the specific sequence/structural motifs that dictate antimicrobial and cytotoxic activities. Perhaps unsurprisingly these activities appear to be dictated by a delicate balance of cationicity, hydrophobicity, amphipathicity, and ultimately the structural characteristics of the peptides. 

As many of the phenotypic changes induced following PhoPQ activation involve host defense peptide resistance characteristics, it is postulated that host defense peptides serve as an endogenous ligand for PhoQ Indeed, the exposure of S. typhimurium to sublethal concentrations of cationic antimicrobial peptides results in activation of the PhoPI regulon and host defense peptide resistance phenotypes. " Supporting... 

Third, that virtually every cationic peptide sequence possesses some degree of antimicrobial activity in vitro suggests that this activity may be a general phenomenon associated with all peptides rather than solely to host defense peptides. Indeed, it has been demonstrated that a threshold amount of hydrophobicity and/or cationicity are sufficient to bestow antimicrobial activity within a peptide. ... 

Host defense peptides are ubiquitous in nature and have been found in every living organism that has been examined for their presence. These short, amphipathic cationic peptides are multifaceted host defense... 

Host defense peptides are ancient effectors of innate immunity found in all organisms, which have evolved several different mechanisms of action (1-3). Many of these peptides display amphipathic, cationic scaffolds that allow... 

Brown, K. L. and Hancock, R. E. (2006) Cationic host defense (antimicrobial) peptides. Curr. Opin. Immunol. 18, 24-30. 

Ova the last two decades, a growing numba of studies have shown that some of the cationic, amphipathic, AMPs, including both natural host defense peptides (HDPs) and s)mthetic AMPs, exhibit a broad spectrum of cytotoxic activity against canca cells. These AMPs can be grouped into two broad... 

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