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An alpha-helical cationic antimicrobial peptide selectively modulates macrophage responses to lipopolysaccharide and directly alters macrophage gene expression. (2000)

by M G Scott, C M Rosenberger, M R Gold, B B Finlay, R E Hancock
Venue:J. Immunol. (Baltimore),
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Antimicrobial peptides: an overview of a promising class of therapeutics DOI: 10.2478/s11535-007-0010-5 Review article

by Andrea Giuliani, Giovanna Pirri, Silvia Fabiole Nicoletto , 2007
"... Abstract: Antibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of t ..."
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Abstract: Antibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of this class of molecules is their ability to kill multidrug-resistant bacteria. Antimicrobial peptides are relatively small (6 to 100 aminoacids), amphipathic molecules of variable length, sequence and structure with activity against a wide range of microorganisms including bacteria, protozoa, yeast, fungi, viruses and even tumor cells. They usually act through relatively non-specific mechanisms resulting in membranolytic activity but they can also stimulate the innate immune response. Several peptides have already entered pre-clinical and clinical trials for the treatment of catheter site infections, cystic fibrosis, acne, wound healing and patients undergoing stem cell transplantation. We review the advantages of these molecules in clinical applications, their disadvantages including their low in vivo stability, high costs of production and the strategies for their discovery and optimization.
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...ration of a capsule as a means of adherence to tissue or avoidance of opsonization and phagocytosis such as the highly anionic capsular exopolysaccharide produced by virulent strains of P. aeruginosa =-=[108]-=-. Attempts at inducing Pexiganan resistance in E. coli and S. aureus by chemical mutagenesis have been up to now unsuccessful. Anyway, population models of the evolutionary genetics of resistance have...

Immunomodulatory activity of small host defense peptides

by Dawn M. E. Bowdish, Donald J. Davidson, Monisha G. Scott, Robert E. W. Hancock, Dawn M. E. Bowdish, Donald J. Davidson, Monisha G. Scott, Robert E. W. Hancock - Antimicrob. Agents Chemother , 2005
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...ent antiendotoxic properties. Certain cationic peptides have the ability to block the production of cytokines produced in response to LPS by either directly up-regulating inhibitory pathways in cells =-=(26)-=- or interfering with the ability of LPS to bind LPS-binding protein (27). THP-1 cells were stimulated with E. coli LPS, and the Downloaded from http://aac.asm.org/ on February 23, 2013 by PENN STATE U...

Innate immune response of oral and foreskin keratinocytes: utilization of different signaling pathways by various bacterial species. Infect. Immun

by Whasun O. Chung, Beverly A. Dale, Whasun O. Chung, Beverly A. Dale , 2004
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...man �-defensins are suspected to play a role in mucosal and skin defenses through their direct antimicrobial action as well as through potential signaling between innate and acquired immune responses =-=(39, 43)-=-. Defensins may act as adjuvants in antibody production (40). Additionally, hBD-2 attracts and stimulates immature dendritic cells via the CCR6 receptor, eventually leading to maturation, activation, ...

Lipopolysaccharide down regulates both scavenger receptor B1 and ATP binding cassette transporter A1 in RAW cells

by Irina Baranova, Tatyana Vishnyakova, Er Bocharov, Zhigang Chen, Alan T. Remaley, John Stonik, Thomas L, Amy P. Patterson, Irina Baranova, Tatyana Vishnyakova, Er Bocharov, Zhigang Chen, Alan T. Remaley, John Stonik, Thomas L. Eggerman, Amy P. Patterson - Infect. Immun , 2002
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...s determined by the fact that the macrophage-like RAW 264.7 cell line is a well-characterized model system in terms of LPS-induced macrophage activation resulting in the proinflammatory cell response =-=(13, 49)-=-. In addition, this cell line is a model widely used in numerous macrophage regulatory studies of cholesterol efflux (48, 51). At the same time, we acknowledge that this cell line (like other models) ...

Effects of acyl versus aminoacyl conjugation on the properties of antimicrobial peptides

by Shahar Rotem, Fadia Zaknoon, Leonid Gaidukov, Arie Dagan, Inna S. Radzishevsky, Shahar Rotem, Fadia Zaknoon, Leonid Gaidukov, Arie Dagan, Amram Mor - Antimicrob. Agents Chemother. 49:2412–2420. 1758 RADZISHEVSKY ET AL. ANTIMICROB. AGENTS CHEMOTHER , 2005
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All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately.
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...ain to be fully understood (18, 25, 45). Antimicrobial peptides also display a variety of interesting properties: they may activate the microbicidal activities of leukocytes and monocytes/macrophages =-=(1, 46, 47)-=-, suppress the production of inflammatory cytokines, offer protection from the cascade of events that lead to endotoxic shock (10, 16, 29), and display synergistic activity in the presence of other pe...

Published Heritage

by Nabil Hayek, Dr. A. Stintzi, Dr. T-f. Mah, Gary W. Slater, Nabil Hayek
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Innate immunity and new adjuvants

by G Mutwiri , V Gerdts , M Lopez , L A Babiuk - Rev Sci Tech , 2007
"... Summary Vaccination remains the most cost-effective biomedical approach to the control of infectious diseases in livestock. Vaccines based on killed pathogens or subunit antigens are safer but are often ineffective and require coadministration with adjuvants to achieve efficacy. Unfortunately, most ..."
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Summary Vaccination remains the most cost-effective biomedical approach to the control of infectious diseases in livestock. Vaccines based on killed pathogens or subunit antigens are safer but are often ineffective and require coadministration with adjuvants to achieve efficacy. Unfortunately, most conventional adjuvants are poorly defined, complex substances that fail to meet the stringent criteria for safety and efficacy desired in new generation vaccines. A new generation of adjuvants that work by activating innate immunity presents exciting opportunities to develop safer, more potent vaccines. In this review the authors highlight the role of innate immunity in protection against infectious disease and provide some examples of promising new adjuvants that activate innate immunity. They do not review the conventional adjuvants present in many vaccines since they have been reviewed extensively previously.
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...9, 12, 36). While the antimicrobial activities of HDP have been known for a long time, recent evidence suggests that at physiological concentrations mammalian HDP have a number of immunomodulatory functions, including recruitment of immature DC and T-cells, glucocorticoid production, macrophage phagocytosis, mast cell degranulation, complement activation, and IL-8 production by epithelial cells (59, 61, 62). Other HDP have been shown to upregulate gene expression in epithelial cells and monocytes, and to neutralise pro-inflammatory cytokine induction and lethality in response to LPS/endotoxin (2, 7, 9, 16, 19, 20, 29, 36, 37, 46, 47). Evidence for the ability of HDP to enhance adaptive immunity (indicative of adjuvant activity) is based on various observations. For example, human neutrophil peptides (HNP) 1 to 3, human beta-defensins 1 and 2, and murine beta-defensins (mBD) have been described to be chemoattractive for immature DC and lymphocytes (4, 60), and monocytes and macrophages (21). Recognition by immature DC occurs through chemokine receptor 6 (4) and other not yet identified receptors (60). Furthermore, in addition to chemoattraction of immature DC, HDP have also been demonstrated to attract mature DC (4, 6, 16)...

Review Characterization of Antimicrobial Peptides toward the Development of Novel Antibiotics

by Wataru Aoki, Mitsuyoshi Ueda , 2013
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pharmaceuticals
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...ibited LPS-induced gelation in the Limulus amoebocyte lysate assay at low concentrations, which indicates a possible application of the peptide as a therapeutic agent for neutralizing endotoxin shock =-=[143]-=-. β-Hairpin AMPs and proline-rich AMPs, such as oncocin (Table 1), have also attracted attention because they predominantly target Gram-negative bacteria [144–146]. Bactenecins, which are members of t...

Serum Stabilities of Short Tryptophan- and Arginine-Rich Antimicrobial Peptide Analogs

by Peptide Analogs, Leonard T. Nguyen, Johnny K. Chau, Nicole A. Perry, Leonie De Boer, Sebastian A. J. Zaat, Hans J
"... Copyright It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content licence (like ..."
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Copyright It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content licence (like
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...g clavinin [27], protegrin [29] and tachyplesin [30]. In fact, some synthetic ahelical peptides have been engineered to be salt-resistant by finetuning the amphipathicity and stability of the a-helix =-=[31,32]-=-. Possible interactions with serum proteins may also impede activity, particularly when the peptides bind to abundant proteins in blood plasma such as human serum albumin (HSA). Recently, a set of cat...

1 MODE OF ACTION STUDIES ON SYNTHETIC ANTIMICROBIAL PEPTIDES MASTER THESIS IN MEDICAL BIOLOGY AND MOLECULAR BIOLOGY

by unknown authors , 2013
"... Increasing prevalence of bacteria that carries resistance towards conventional antibiotics has prompted the investigation into new compounds for bacterial intervention to ensure efficient infection control in the future. One group of potential lead structures for antibiotics is antimicrobial peptide ..."
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Increasing prevalence of bacteria that carries resistance towards conventional antibiotics has prompted the investigation into new compounds for bacterial intervention to ensure efficient infection control in the future. One group of potential lead structures for antibiotics is antimicrobial peptides (AMPs) due to their characteristics as naturally derived compounds with antimicrobial activity. In that perspective, this thesis seeks to characterize the mechanism of action of small library of in silico optimized peptides. Following determination of peptide activity against E.coli, S.aureus and P.aeruginosa, toxicity was assessed revealing meaningful therapeutic indexes for the far majority of the peptides. Investigation of the peptides effect on bacteria uncovered rapid inhibition with signs of bacterial lysis together with increased bacterial size. Both visual and quantitative assays clearly demonstrated bacterial membrane disruption after 10 minutes, although signs of reestablished membrane integrity at lower concentrations were observed after two hours. The membrane disrupting effect was verified by measuring the release of calcein from bacterial mimicking liposomes. This uncovered the most active peptides as inducers of immediate release, indicating the kinetics of membrane permeabilization as an important determinant of bacterial activity. No secondary structure of peptides in the presence of different liposomes was observed, implying that this feature is not essential for bacterial and cytotoxic activity within this library of peptides. In conjunction, these findings provide strong indications of membrane disruption as the primary mechanism of bacterial inhibition for the tested peptides. RESUMÉ En stadig stigende forekomst af bakterier med resistens overfor konventionelle antibiotika har
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