Structuring and interactions of human β‐defensins 2 and 3 with model membranes

Morgera, Francesca; Antcheva, Nikolinka; Pacor, Sabrina; Quaroni, Luca; Berti, Federico; Vaccari, Lisa; Tossi, Alessandro

doi:10.1002/psc.981

Cited by 45 publications

(45 citation statements)

References 15 publications

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“…hBD3 probably interacts with membranes as a dimer forming a platform which remains floating on the surface with two long helices underneath sinking into the membrane interface (26). Consistent with such a model, we recently obtained evidence that hBD3 may not cause membrane disruption in Staphylococcus aureus but rather may interfere with the cell wall biosynthesis machinery (30,38).…”

supporting

confidence: 63%

Human β-Defensin 3 Inhibits Cell Wall Biosynthesis in Staphylococci

et al. 2010

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supporting

confidence: 63%

Human β-Defensin 3 Inhibits Cell Wall Biosynthesis in Staphylococci

et al. 2010

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“…If both mammalian and invertebrate antibacterial defensins have a similar target, what makes the invertebrate defensins so selective toward Gram-positive bacteria? One hypothesis is that unlike invertebrate antibacterial defensins, which require lipid II to be readily accessible, mammalian defensins could use their membrane-disrupting properties (40,41) to gain access to lipid II. Indeed, the membrane activity of invertebrate defensins appears much weaker than that of mammalian defensins.…”

Section: Discussionmentioning

confidence: 99%

Insight into Invertebrate Defensin Mechanism of Action

Schmitt

Wilmes

Pugnière

et al. 2010

Journal of Biological Chemistry

121

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Three oyster defensin variants (Cg-Defh1, Cg-Defh2, and CgDefm) were produced as recombinant peptides and characterized in terms of activities and mechanism of action. In agreement with their spectrum of activity almost specifically directed against Gram-positive bacteria, oyster defensins were shown here to be specific inhibitors of a bacterial biosynthesis pathway rather than mere membrane-active agents. Indeed, at lethal concentrations, the three defensins did not compromise Staphylococcus aureus membrane integrity but inhibited the cell wall biosynthesis as indicated by the accumulation of the UDP-Nacetylmuramyl-pentapeptide cell wall precursor. In addition, a combination of antagonization assays, thin layer chromatography, and surface plasmon resonance measurements showed that oyster defensins bind almost irreversibly to the lipid II peptidoglycan precursor, thereby inhibiting the cell wall biosynthesis. To our knowledge, this is the first detailed analysis of the mechanism of action of antibacterial defensins produced by invertebrates. Interestingly, the three defensins, which were chosen as representative of the oyster defensin molecular diversity, bound differentially to lipid II. This correlated with their differential antibacterial activities. From our experimental data and the analysis of oyster defensin sequence diversity, we propose that oyster defensin activity results from selective forces that have conserved residues involved in lipid II binding and diversified residues at the surface of oyster defensins that could improve electrostatic interactions with the bacterial membranes.

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“…Like other cationic peptides, defensins rapidly and efficiently permeabilize membrane bilayers (21,22) and also appear to inhibit bacterial cell wall biosynthesis (19,23). In mammals, the peptides are produced in cells and tissues such as salivary glands and Paneth cells and are secreted into tissues that come into contact with invading microbes, for example, the buccal cavity and the intestinal lining (24,25).…”

Section: Importancementioning

confidence: 99%

Comparative Analysis of the Antimicrobial Activities of Plant Defensin-Like and Ultrashort Peptides against Food-Spoiling Bacteria

Kraszewska

Beckett

James

et al. 2016

Appl Environ Microbiol

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Antimicrobial peptides offer potential as novel therapeutics to combat food spoilage and poisoning caused by pathogenic and nonpathogenic bacteria. Our previous studies identified the peptide human beta-defensin 3 (HBD3) as a potent antimicrobial agent against a wide range of beer-spoiling bacteria. Thus, HBD3 is an excellent candidate for development as an additive to prevent food and beverage spoilage. To expand the repertoire of peptides with antimicrobial activity against bacteria associated with food spoilage and/or food poisoning, we carried out an in silico discovery pipeline to identify peptides with structure and activity similar to those of HBD3, focusing on peptides of plant origin. Using a standardized assay, we compared the antimicrobial activities of nine defensin-like plant peptides to the activity of HBD3. Only two of the peptides, fabatin-2 and Cp-thionin-2, displayed antimicrobial activity; however, the peptides differed from HBD3 in being sensitive to salt and were thermostable. We also compared the activities of several ultrashort peptides to that of HBD3. One of the peptides, the synthetic tetrapeptide O3TR, displayed biphasic antimicrobial activity but had a narrower host range than HBD3. Finally, to determine if the peptides might act in concert to improve antimicrobial activity, we compared the activities of the peptides in pairwise combinations. The plant defensin-like peptides fabatin-2 and Cp-thionin-2 displayed a synergistic effect with HBD3, while O3TR was antagonistic. Thus, some plant defensin-like peptides are effective antimicrobials and may act in concert with HBD3 to control bacteria associated with food spoilage and food poisoning. IMPORTANCEFood spoilage and food poisoning caused by bacteria can have major health and economic implications for human society. With the rise in resistance to conventional antibiotics, there is a need to identify new antimicrobials to combat these outbreaks in our food supply. Here we screened plant peptide databases to identify peptides that share structural similarity with the human defensin peptide HBD3, which has known antimicrobial activity against food-spoiling bacteria. We show that two of the plant peptides display antimicrobial activity against bacteria associated with food spoilage. When combined with HBD3, the peptides are highly effective. We also analyzed the activity of an easily made ultrashort synthetic peptide, O3TR. We show that this small peptide also displays antimicrobial activity against food-spoiling bacteria but is not as effective as HBD3 or the plant peptides. The plant peptides identified are good candidates for development as natural additives to prevent food spoilage.A ntimicrobial peptides (AMPs) are short oligopeptides ranging from 4 to 100 amino acids that display antimicrobial activity against a broad range of pathogens, including Gram-positive and -negative bacteria, fungi, viruses, protists, parasites, and even insects (1). AMPs form part of the innate immune response, acting as a first line of defense and...

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Structuring and interactions of human β‐defensins 2 and 3 with model membranes

Cited by 45 publications

References 15 publications

Human β-Defensin 3 Inhibits Cell Wall Biosynthesis in Staphylococci

Human β-Defensin 3 Inhibits Cell Wall Biosynthesis in Staphylococci

Insight into Invertebrate Defensin Mechanism of Action

Comparative Analysis of the Antimicrobial Activities of Plant Defensin-Like and Ultrashort Peptides against Food-Spoiling Bacteria

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