Insights into the mechanisms of action of host defence peptides from biophysical and structural investigations

Bechinger, Burkhard

doi:10.1002/psc.1343

Cited by 79 publications

(57 citation statements)

References 138 publications

(206 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported the relative preference of barrel-stave versus toroidal mechanism depends on peptide length (57, 75, 92–94). Modifications of the peptide sequence involving changes in charge distribution, hydrophobicities, and surface areas of different amino acid side-chains have been shown to modulate the specificities and mechanisms of action for AMPs (49, 53, 70, 95, 96). …”

Section: Proposed Mechanisms Of Actionmentioning

confidence: 99%

On the Role of NMR Spectroscopy for Characterization of Antimicrobial Peptides

et al. 2013

View full text Add to dashboard Cite

Summary Antimicrobial peptides (AMPs) provide a primordial source of immunity, conferring upon eukaryotic cells resistance against bacteria, protozoa, and viruses. Despite a few examples of anionic peptides, AMPs are usually relatively short positively charged polypeptides, consisting of a dozen to about a hundred amino acids, and exhibiting amphipathic character. Despite significant differences in their primary and secondary structures, all AMPs discovered to date share the ability to interact with cellular membranes, thereby affecting bilayer stability, disrupting membrane organization, and/or forming well-defined pores. AMPs selectively target infectious agents without being susceptible to any of the common pathways by which these acquire resistance, thereby making AMPs prime candidates to provide therapeutic alternatives to conventional drugs. However, the mechanisms of AMP actions are still a matter of intense debate. The structure-function paradigm suggests that a better understanding of how AMPs elicit their biological functions could result from atomic resolution studies of peptide-lipid interactions. In contrast, more strict thermodynamic views preclude any roles for three-dimensional structures. Indeed, the design of selective AMPs based soley on structural parameters has been challenging. In this chapter, we will focus on selected AMPs for which studies on the corresponding AMP-lipid interactions have helped reach an understanding of how AMP effects are mediated. We will emphasize the roles of both liquid- and solid-state NMR spectroscopy for elucidating the mechanisms of action of AMPs.

show abstract

Section: Proposed Mechanisms Of Actionmentioning

confidence: 99%

On the Role of NMR Spectroscopy for Characterization of Antimicrobial Peptides

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The mechanisms by which CAMPs mediate their effect, however, remain unclear and controversial. Several recent reviews have summarized different models proposed to explain the CAMP mechanism of action (1,(4)(5)(6)(7). These models fall into two categories, transmembrane pore formation models (e.g., barrel stave or toroidal) and non-pore-based models (which include the carpet model and the detergent-like model).…”

mentioning

confidence: 99%

Chemical Genomic Screening of a Saccharomyces cerevisiae Genomewide Mutant Collection Reveals Genes Required for Defense against Four Antimicrobial Peptides Derived from Proteins Found in Human Saliva

Lis

Bhatt

Schoenly

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

To compare the effects of four antimicrobial peptides (MUC7 12-mer, histatin 12-mer, cathelicidin KR20, and a peptide containing lactoferricin amino acids 1 to 11) on the yeast Saccharomyces cerevisiae, we employed a genomewide fitness screen of combined collections of mutants with homozygous deletions of nonessential genes and heterozygous deletions of essential genes. When an arbitrary fitness score cutoffs of 1 (indicating a fitness defect, or hypersensitivity) and ؊1 (indicating a fitness gain, or resistance) was used, 425 of the 5,902 mutants tested exhibited altered fitness when treated with at least one peptide. Functional analysis of the 425 strains revealed enrichment among the identified deletions in gene groups associated with the Gene Ontology (GO) terms "ribosomal subunit," "ribosome biogenesis," "protein glycosylation," "vacuolar transport," "Golgi vesicle transport," "negative regulation of transcription," and others. Fitness profiles of all four tested peptides were highly similar, particularly among mutant strains exhibiting the greatest fitness defects. The latter group included deletions in several genes involved in induction of the RIM101 signaling pathway, including several components of the ESCRT sorting machinery. The RIM101 signaling regulates response of yeasts to alkaline and neutral pH and high salts, and our data indicate that this pathway also plays a prominent role in regulating protective measures against all four tested peptides. In summary, the results of the chemical genomic screens of S. cerevisiae mutant collection suggest that the four antimicrobial peptides, despite their differences in structure and physical properties, share many interactions with S. cerevisiae cells and consequently a high degree of similarity between their modes of action. C ationic antimicrobial peptides (CAMPs) are small positively charged peptides, active against a broad range of microorganisms, including bacteria, fungi, viruses, and parasites (1-3). Because of their broad spectrum of activity, they have been considered promising alternatives to conventional antimicrobial agents. The mechanisms by which CAMPs mediate their effect, however, remain unclear and controversial. Several recent reviews have summarized different models proposed to explain the CAMP mechanism of action (1, 4-7). These models fall into two categories, transmembrane pore formation models (e.g., barrel stave or toroidal) and non-pore-based models (which include the carpet model and the detergent-like model). Both involve peptide-induced membrane permeabilization/disruption of target cells, leading to membrane depolarization, loss of vital ions and other cellular components, and ultimately lysis and cell death. There is, however, a growing acceptance that CAMPs also operate through interactions with intracellular targets or via disruption of key intracellular processes (reviewed in reference 6). In this scenario, the peptides cross the microbial membranes without significant disruption of the membrane. Finally, some peptides have ...

show abstract

“…In fact, the structure of the antimicrobial peptide and its activity are governed by its degree of cationization (positive charge content), amphiphilic characteristics, hydrophobic characteristics, structural tendency, amino acid sequence composition, angular degree, and amphiphilic balance, or cation/hydrophobic balance, that is the optimum ratio between the number of cations and the peptide’s hydrophobicity (Yeaman and Yount 2003; Barker et al 2000; Zasloff et al 1988; Takahashi et al 2010; Bechinger 2011; Palermo and Kuroda 2010). To further clarify the relationships between these primary structure parameters and the antimicrobial activities of the peptides, high-throughput methods such as combinatorial chemistry (Hilpert et al 2006; Fjell et al 2012) should be helpful.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial activity identification of pCM19 and pCM12 derived from hGlyrichin

Sha

Zhang

2016

SpringerPlus

View full text Add to dashboard Cite

Background: hGlyrichin is a novel human antimicrobial peptide rich in glycine. The previous study of known human antimicrobial peptides indicated that in an eligible range, the greater corresponding antibacterial activity was consisted with the shorter peptide sequence.Findings: Two peptides named pCM19 and pCM12 were synthesized and the antibacterial activity assay results showed that these peptides exhibited strong antibacterial activity that was inversely proportional to the length of the peptide. Despite the effective inhibition of bacterial growth, the synthetic peptides showed no hemolytic effect on human red blood cells. Conclusions:Taken together, these two peptides derived from hGlyrichin both have strong antibacterial activity and are not toxic to human somatic cells.

show abstract

Insights into the mechanisms of action of host defence peptides from biophysical and structural investigations

Abstract: Structures of eleven zervamicin and two emerimicin peptide antibiotics studied by fast atom bombardment mass spectrometry.

Cited by 79 publications

References 138 publications

On the Role of NMR Spectroscopy for Characterization of Antimicrobial Peptides

On the Role of NMR Spectroscopy for Characterization of Antimicrobial Peptides

Chemical Genomic Screening of a Saccharomyces cerevisiae Genomewide Mutant Collection Reveals Genes Required for Defense against Four Antimicrobial Peptides Derived from Proteins Found in Human Saliva

Antibacterial activity identification of pCM19 and pCM12 derived from hGlyrichin

Contact Info

Product

Resources

About