The Roles of Antimicrobial Peptides in Innate Host Defense

Diamond, Gill; Beckloff, Nicholas; Weinberg, Aaron; Kisich, Kevin O.

doi:10.2174/138161209788682325

Cited by 549 publications

(446 citation statements)

References 247 publications

(259 reference statements)

Supporting

Mentioning

434

Contrasting

Unclassified

Order By: Relevance

“…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%

“…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.…”

mentioning

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.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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.

View full text Add to dashboard Cite

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...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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.

View full text Add to dashboard Cite

show abstract

“…The direct antibiotic activity of AMPs is thought to be based on their cationic and amphiphilic nature, which enables these peptides to interact with negatively charged bacterial surfaces and membranes, subsequently causing membrane disruption or altering metabolic processes (Brogden, 2005;Hale and Hancock, 2007). AMPs represent potential substitutes for antibiotics due to their broad specificity against bacteria or fungi, and their anti-viral, anti-tumoral, anti-inflammatory, wound-healing, and immunomodulatory activities (Diamond et al, 2009;Otero-González et al, 2010). Despite being evolutionary ancient, AMPs exhibit great diversity in terms of structural features, biological properties and functions, and also in their tissue distribution and expression profiles (Bachere et al, 2004;Bulet et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

A defensin from clam Venerupis philippinarum: Molecular characterization, localization, antibacterial activity, and mechanism of action

Zhang

Yang

Wang

et al. 2015

Developmental & Comparative Immunology

View full text Add to dashboard Cite

A B S T R A C TAntimicrobial peptides (AMPs) are important mediators of the primary host defense system against microbial invasion. In the present study, we cloned and characterized a member of the invertebrate defensin from the clam Venerupis philippinarum, designated VpDef. Amino acid sequence analysis showed that VpDef was similar to defensins from marine mollusks and ticks. In non-stimulated clams, RT-PCR and immunohistochemical analysis revealed that both VpDef mRNA and the encoding peptide were constitutively expressed in hemocytes and mantles, as well as in other major tissues. VpDef transcripts were significantly induced in hemocytes at different time intervals post Vibrio anguillarum infection. The recombinant VpDef (rVpDef) showed the highest activity against Gram-positive bacteria Micrococcus luteus and less effective to Gram-negative bacteria. In addition, incubation of rVpDef with M. luteus at 1 × and 3 × MIC could induce an obvious decrease of the membrane potential and notable changes of membrane permeability in a dose-dependent manner. Membrane integrity and bacterial viability analysis also revealed that rVpDef increased the membrane permeability of M. luteus and then resulted in cell death at 2 × and 10 × MIC. Overall, these results suggest that VpDef has an important function in host defense against invasive pathogens, probably killing microbes by inducing membrane lesions.

show abstract

“…Host defence peptides (HDPs) have emerged as potential candidates (Zasloff, 2002; Diamond et al ., 2009; Rathinakumar et al ., 2009). The modes of action of HDPs vary among different types; however, many HDPs have been shown to possess the ability to disrupt bacterial membrane (Oren and Shai, 1997; Oren et al ., 2002; Zasloff, 2002; Rathinakumar et al ., 2009).…”

Section: Introductionmentioning

confidence: 99%

Random peptide mixtures as new crop protection agents

Topman

Tamir‐Ariel

Bochnic-Tamir

et al. 2018

Microbial Biotechnology

View full text Add to dashboard Cite

SummaryMany types of crops are severely affected by at least one important bacterial disease. Chemical control of bacterial plant diseases in the field vastly relies on copper‐based bactericides, yet with limited efficacy. In this study, we explored the potential of two random peptide mixture (RPM) models as novel crop protection agents. These unique peptide mixtures consist of random combination of l‐phenylalanine and l‐ or d‐lysine (FK‐20 and FdK‐20, respectively) along the 20 mer chain length of the peptides. Both RPMs displayed powerful bacteriostatic and bactericidal activities towards strains belonging to several plant pathogenic bacterial genera, for example, Xanthomonas, Clavibacter and Pseudomonas. In planta studies in the glasshouse revealed that RPMs significantly reduced disease severity of tomato and kohlrabi plants infected with Xanthomonas perforans and Xanthomonas campestris pv. campestris respectively. Moreover, RPM effects on reduction in disease severity were similar to those exerted by the commercial copper‐based bactericide Kocide 2000 that was applied at a 12‐fold higher concentration of the active compound relative to the RPM treatments. Importantly, the two tested RPM compounds had no toxic effect on survival of bees and Caco‐2 mammalian cells. This study demonstrates the potential of these innovative RPMs to serve as crop protection agents against crop diseases caused by phytopathogenic bacteria.

show abstract

The Roles of Antimicrobial Peptides in Innate Host Defense

Cited by 549 publications

References 247 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

A defensin from clam Venerupis philippinarum: Molecular characterization, localization, antibacterial activity, and mechanism of action

Random peptide mixtures as new crop protection agents

Contact Info

Product

Resources

About