Interaction of Antimicrobial Peptides with Lipopolysaccharides

Ding, Lai; Yang, Lin; Weiß, Thomas; Waring, Alan J.; Lehrer, Robert I.; Huang, Huey W.

doi:10.1021/bi035130+

Cited by 100 publications

(119 citation statements)

References 42 publications

(90 reference statements)

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“…Interaction with the outer leaflet represents in most cases a crucial step to accomplish the peptide antimicrobial activity, although other mechanisms accounting for peptide antimicrobial activity have been proposed [43,48]. Therefore, structural investigations of antimicrobial peptides in complex with LPS, a major component of the bacterial membranes, are essential to fully understand their mechanism of action [49,50].…”

Section: Discussionmentioning

confidence: 99%

Design, structural and functional characterization of a Temporin-1b analog active against Gram-negative bacteria

Avitabile

Netti

Orefice

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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Conclusion:Our results show that it is possible to widen the activity spectrum of an antimicrobial peptide by subtle changes of the primary structure. TB_KKG6A, having a simple composition, broad spectrum of antimicrobial activity and a very low hemolytic activity, is a promising candidate for the design of novel antimicrobial peptides. General significance:The activity of antimicrobial peptides is strongly related to the ability of the peptide to interact and break the bacterial membrane. Our studies on TB_KKG6A indicate that efficient interactions with LPS can be achieved when the peptide is not perfectly amphipatic, since this feature seems to help the toroidal pores formation process. Highlights A new Temporin B analogue, TB_KKG6A, was designed.TB_KKG6A is active against Gram-positive and Gram-negative bacteria.The peptide strongly interacts with the LPS of E.coli.The peptide folds into a kinked helix upon interaction with LPS. The peptide shows very low hemolytic activity.

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Section: Discussionmentioning

confidence: 99%

Design, structural and functional characterization of a Temporin-1b analog active against Gram-negative bacteria

Avitabile

Netti

Orefice

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…The increase in surface roughness may have been caused by peptide incorporation into the LPS-containing outer membrane (7,17), causing a "crumpling" effect due to an increase in surface area. The lesions may have been caused by either peptide aggregates (19,30), the release of LPS-containing vesicles (17), or even autolytic reactions (1,9).…”

Section: Discussionmentioning

confidence: 99%

Atomic Force Microscopy Study of the Effect of Antimicrobial Peptides on the Cell Envelope of Escherichia coli

Meincken

Holroyd

Rautenbach

2005

Antimicrob Agents Chemother

166

126

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The influences of the antibacterial magainin 2 and PGLa from the African clawed frog (Xenopus laevis) and the hemolytic bee venom melittin on Escherichia coli as the target cell were studied by atomic force microscopy (AFM). Nanometer-scale images of the effects of the peptides on this gram-negative bacterium's cell envelope were obtained in situ without the use of fixing agents. These high-resolution AFM images of the surviving and intact target cells before and after peptide treatment showed distinct changes in cell envelope morphology as a consequence of peptide action. Although all three peptides are lytic to E. coli, it is clear from this AFM study that each peptide causes distinct morphological changes in the outer membrane and in some cases the inner membrane, probably as a consequence of different mechanisms of action.Bacterial resistance to conventional antibiotics has become a major problem worldwide, and certain strains of bacteria are already resistant to all available drugs (3, 29). The development of a new family of antibiotics is therefore an important research topic. Antimicrobial peptides are considered good candidates for the next group of antibiotics because their proposed mode of action is different from those of conventional antibiotics (12,25). To advance antimicrobial peptides to the status of a new group of antibiotics, it is important to understand the mechanisms of action of these agents and the reason for their selectivity against microbes. In this study we compared the actions of three different peptides, namely, melittin, the toxic and hemolytic 26-residue peptide from the European honeybee Apis mellifera (6, 11), and two antibacterial peptides from the African clawed frog Xenopus laevis, an amide analogue of the 23-residue magainin 2 (32, 33) and the 21-residue PGLa (28), on the membrane of Escherichia coli. All three peptides are cationic ␣-helical antimicrobial peptides with markedly different sequential distributions of polar and nonpolar amino acids. However, all three peptides are amphipathic and highly membranolytic, with PGLa and magainin 2 having a better selectivity, via electrostatic discrimination, toward prokaryotic cells (13, 22) than the hemolytic melittin (which is a nonselective lytic peptide).Model membrane studies have provided a good understanding of antimicrobial peptides and their mechanisms of action. Different models for the interaction of a peptide with the bacterial membrane have been proposed: the barrel stave model (2), the toroidal pore or wormhole model (5, 31), the carpet model (23), and the peptide aggregate model (19,30). Most antimicrobial peptides are thought to follow the toroidal pore model and/or carpet model and not the barrel stave model, in which the peptides in the pore need to span the membrane without deformation of the lipid bilayer. Peptides that form toroidal pores remain associated with the phospholipid head groups and insert perpendicularly to the membrane plane by causing the lipid bilayer to fold back on itself. It has been proposed ...

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“…LPS molecules are the major targets of cationic peptides that, most commonly, form disrupting channels in the outer membrane of Gramnegative bacteria and gain access to the plasma membrane (41). Thus, the stability of the outer membrane depends mainly on the good arrangement of the LPS, which is known to involve ionic interactions with bivalent cations (26).…”

Section: Discussionmentioning

confidence: 99%

Truncation of the Lipopolysaccharide Outer Core Affects Susceptibility to Antimicrobial Peptides and Virulence of Actinobacillus pleuropneumoniae Serotype 1

Ramjeet

Deslandes

Michael

et al. 2005

Journal of Biological Chemistry

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We reported previously that the core oligosaccharide region of the lipopolysaccharide (LPS) is essential for optimal adhesion of Actinobacillus pleuropneumoniae, an important swine pathogen, to respiratory tract cells. Rough LPS and core LPS mutants of A. pleuropneumoniae serotype 1 were generated by using a mini-Tn10 transposon mutagenesis system. Here we performed a structural analysis of the oligosaccharide region of three core LPS mutants that still produce the same O-antigen by using methylation analyses and mass spectrometry. We also performed a kinetic study of proinflammatory cytokines production such as interleukin (IL)-6, tumor necrosis factor-␣, IL1-␤, MCP-1, and IL8 by LPS-stimulated porcine alveolar macrophages, which showed that purified LPS of the parent strain, the rough LPS and core LPS mutants, had the same ability to stimulate the production of cytokines. Most interestingly, an in vitro susceptibility test of these LPS mutants to antimicrobial peptides showed that the three core LPS mutants were more susceptible to cationic peptides than both the rough LPS mutant and the wild type parent strain. Furthermore, experimental pig infections with these mutants revealed that the galactose (Gal I) and D,D-heptose (Hep IV) residues present in the outer core of A. pleuropneumoniae serotype 1 LPS are important for adhesion and overall virulence in the natural host, whereas deletion of the terminal GalNAc-Gal II disaccharide had no effect. Our data suggest that an intact core-lipid A region is required for optimal protection of A. pleuropneumoniae against cationic peptides and that deletion of specific residues in the outer LPS core results in the attenuation of the virulence of A. pleuropneumoniae serotype 1.

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Interaction of Antimicrobial Peptides with Lipopolysaccharides

Cited by 100 publications

References 42 publications

Design, structural and functional characterization of a Temporin-1b analog active against Gram-negative bacteria

Design, structural and functional characterization of a Temporin-1b analog active against Gram-negative bacteria

Atomic Force Microscopy Study of the Effect of Antimicrobial Peptides on the Cell Envelope of Escherichia coli

Truncation of the Lipopolysaccharide Outer Core Affects Susceptibility to Antimicrobial Peptides and Virulence of Actinobacillus pleuropneumoniae Serotype 1

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