Peptide Antimicrobial Agents

Jenssen, Håvard; Hamill, Pamela; Hancock, Robert E. W.

doi:10.1128/cmr.00056-05

Cited by 2,123 publications

(2,041 citation statements)

References 286 publications

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“…This particular DPC/SDS molar ratio was chosen to be close to that between zwitterionic and negatively charged lipids typical for the inner membrane of Gram-negative bacteria. 25 Table S1 reports the 1 H and 13 C resonance assignments for Esc (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) in the presence of either DPC or DPC/SDS micelles, obtained through a set of two-dimensional homo-and heteronuclear experiments, namely, DQF-COSY, TOCSY, NOESY, and HSQC. Figures 1a and 1b show the deviations of the observed chemical shifts from the reference "random coil" values for 1 H and 13 C, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…8 Several recent articles have reviewed in detail the different modes of action postulated for AMPs. [9][10][11] The amphipathic conformation adopted by the AMP, with the hydrophilic residues interacting with the polar head groups of the phospholipids and the water molecules, and the hydrophobic residues being protected from water contacts by inserting into the lipid bilayer core, is considered essential for it to exert the antimicrobial activity. Also the net positive charge plays a fundamental role.…”

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confidence: 99%

“…23 A globally amphipathic structure was found, with a helical conformation for the N-terminal portion (encompassing the first 12 residues) and an unfolded C-terminal fragment. 23 However, as the H 2 O/TFE solvent is an isotropic environment, such a structural model for Esc (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) should be taken with caution. Despite promoting peptide folding by favoring intramolecular H-bonds, indeed, H 2 O/TFE mixtures inherently lack the intrinsic anisotropic character of a lipid bilayer.…”

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confidence: 99%

“…In particular, both zwitterionic and negatively charged micelles have been employed to model eukaryotic and prokaryotic plasma membrane, respectively, as bacterial membranes are usually characterized by a higher content of negatively charged lipids than the former. 6,12,13 The insertion depth of Esc (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) into the micelles was estimated by using Mn 2+ ions as a paramagnetic probe. The results clearly confirm the helical folding of Esc (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) and show how binding and folding are prominent only in the presence of a negatively charged membrane.…”

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confidence: 99%

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Folded Structure and Insertion Depth of the Frog-Skin Antimicrobial Peptide Esculentin-1b(1–18) in the Presence of Differently Charged Membrane-Mimicking Micelles

Manzo¹,

Casu²,

Rinaldi³

et al. 2014

J. Nat. Prod.

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Antimicrobial peptides (AMPs) are effectors of the innate immunity of most organisms. Their role in the defense against pathogen attack and their high selectivity for bacterial cells make them attractive for the development of a new class of antimicrobial drugs. The N-terminal fragment of the frog-skin peptide esculentin-1b (Esc(1-18)) has shown broad spectrum antimicrobial activity.Similarly to most cationic AMPs, it is supposed to act by binding to and damaging the negatively charged plasma-membrane of bacteria. Differently from many other AMPs, Esc(1-18) activity is preserved in biological fluids such as serum. In this work, a structural investigation was performed through NMR spectroscopy. The 3D structure was obtained in the presence of either zwitterionic or negatively charged micelles as membrane models for eukaryotic and prokaryotic membranes, respectively. Esc(1-18) showed a higher affinity for and deeper insertion into the latter, and adopted an amphipathic helical structure characterized by a kink at the residue G8. These findings were confirmed by measuring penetration into lipid monolayers. The presence of negatively charged lipids in the bilayer appears to be necessary for Esc(1-18) to bind, fold in the right threedimensional structure and, ultimately, to exert its biological role as an AMP. 3The lack of a new class of antibiotics is an urgent problem, as many important pathogens are rapidly developing resistance to most of the clinically usable antibiotics. 1,2 Clinical impact of antibiotic resistance is immense, with increasing length of hospital stay, costs and mortality. 3,4 Antimicrobial peptides (AMPs) have attracted the interest of the scientific community as promising candidates for the development of a new class of antimicrobial drugs. They are part of the innate immune system of the majority of the multicellular organisms, and are typically characterized by a wide spectrum of antimicrobial activity, from Gram-negative to Gram-positive bacteria, fungi, protozoa and enveloped viruses. [5][6][7] Despite amino acid sequence homology is not high, AMPs share some common features. They are relatively short (< 60 residues), cationic, have a large content (≥ 50%) of hydrophobic residues and adopt an amphipathic three-dimensional folding when interacting with pathogens" membranes. 6 Generally, AMPs destroy or permeate the microbial plasma-membrane. The membrane is formed through evolutionarily well conserved biosynthetic processes and represents a non-selective target, making modifications by the microorganisms difficult and, thus, resistance onset is unlikely. 8 Several recent articles have reviewed in detail the different modes of action postulated for AMPs. [9][10][11] The amphipathic conformation adopted by the AMP, with the hydrophilic residues interacting with the polar head groups of the phospholipids and the water molecules, and the hydrophobic residues being protected from water contacts by inserting into the lipid bilayer core, is considered essential for it to exert the antimicro...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Folded Structure and Insertion Depth of the Frog-Skin Antimicrobial Peptide Esculentin-1b(1–18) in the Presence of Differently Charged Membrane-Mimicking Micelles

Manzo¹,

Casu²,

Rinaldi³

et al. 2014

J. Nat. Prod.

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“…The main role attributed to these peptides is their direct biocidal actions towards bacteria, fungi, and parasites. However, the importance of the host defence activity depends on the site specificity of action within each organism (Jenssen et al 2006).…”

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confidence: 99%

Peptides as toxins/defensins

Palma

2010

Amino Acids

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Rondonin: antimicrobial properties and mechanism of action

et al. 2021

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Infectious diseases are among the major causes of death in the human population. A wide variety of organisms produce antimicrobial peptides (AMPs) as part of their first line of defense. A peptide from Acanthoscurria rondoniae plasma, rondonin -with antifungal activity, a molecular mass of 1,236 Da and primary sequence IIIQYEGHKH -was previously studied (Uniprot accession number B3EWP8). It showed identity with the C-terminus of subunit "D" of the hemocyanin of the Aphonopelma hentzi spider. This result led us to propose a new pathway of the immune system of arachnids that suggests a new function to hemocyanin: production of antimicrobial peptides.Rondonin does not interact with model membranes and was able to bind to yeast nucleic acids but not bacteria. It was not cytotoxic against mammalian cells. The antifungal activity of rondonin is pH dependent and peaks at pH ~4-5. The peptide presents synergism with Gomesin (spider hemocyte antimicrobial peptide -UniProtKB -P82358) against human yeast pathogens, suggesting a new potential alternative treatment option. Antiviral activity was detected against RNA viruses, measles, H1N1 and encephalomyocarditis. This is the first report of an arthropod hemocyanin fragment with activity against human viruses. Currently, it is vital to invest in the search for natural and synthetic antimicrobial compounds that, above all, present alternative mechanisms of action to first-choice antimicrobials.

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Peptide Antimicrobial Agents

Cited by 2,123 publications

References 286 publications

Folded Structure and Insertion Depth of the Frog-Skin Antimicrobial Peptide Esculentin-1b(1–18) in the Presence of Differently Charged Membrane-Mimicking Micelles

Folded Structure and Insertion Depth of the Frog-Skin Antimicrobial Peptide Esculentin-1b(1–18) in the Presence of Differently Charged Membrane-Mimicking Micelles

Peptides as toxins/defensins

Rondonin: antimicrobial properties and mechanism of action

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