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Animals and higher plants express endogenous peptide antibiotics called defensins. These small cysteine-rich peptides are active against bacteria, fungi and viruses. Here we describe plectasin-the first defensin to be isolated from a fungus, the saprophytic ascomycete Pseudoplectania nigrella. Plectasin has primary, secondary and tertiary structures that(More)
We examined human tears for molecules that killed gram-positive bacteria. The principal mediator of bactericidal activity against staphylococci proved to be a calcium-dependent enzyme, secretory phospholipase A2. Whereas the concentration of secretory phospholipase A2 in the normal tear film exceeded 30 microg/ml, only 1.1 ng (<0.1 nM) of the enzyme per ml(More)
We examined the activity of defensins, cysteine-rich cationic peptides that are abundant in the cytoplasmic granules of human and rabbit granulocytes, against various tumor targets. The three human defensins, HNP-1, HNP-2, and HNP-3, lysed human and murine targets in chromium release and dye exclusion assays. Defensin-mediated tumor cell lysis was(More)
We examined the secretion of antimicrobial proteins and peptides into surgically isolated and continuously perfused segments of rat small intestine. Up to nine discrete antimicrobial molecules appeared in the intestinal perfusates following intravenous administration of bethanechol, a cholinergic agonist, or intralumenal instillation of lipopolysaccharide(More)
The therapeutic, antibiotic potential of antimicrobial peptides can be prohibitively diminished because of the cytotoxicity and hemolytic profiles they exhibit. Quantifying and predicting antimicrobial peptide toxicity against host cells is thus an important goal of AMP related research. In this work, we present quantitative structure activity relationships(More)
Membrane pores spontaneously formed by antimicrobial peptides in membranes were crystallized for the first time by manipulating the sample hydration and temperature. Neutron diffraction shows that magainins and protegrins form stable pores in fully hydrated fluid membranes. At lower hydration levels or low temperature, the membrane multilayers crystallize.(More)
Antimicrobial peptides (AMPs), important effector molecules of the innate immune system, also provide templates for designing novel antibiotics. Protegrin, an especially potent AMP found in porcine leukocytes, was recently shown to form octameric transmembrane pores. We have employed a combination of experiments and models spanning length scales from the(More)
Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords(More)
Clavanins are histidine-rich, amidated alpha-helical antimicrobial peptides that were originally isolated from the leukocytes (hemocytes) of a tunicate, Styela clava. The activities of clavanin A amide and clavanin A acid against Escherichia coli, Listeria monocytogenes, and Candida albicans were substantially greater at pH 5.5 than at pH 7.4. In contrast,(More)