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      Antimicrobial Peptides: An Emerging Category of Therapeutic Agents

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          Abstract

          Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

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          Most cited references121

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          Antimicrobial peptides of multicellular organisms.

          Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?
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            Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?

            Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant and animal species. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of antimicrobial peptide activity, their relevance to how peptides damage and kill microorganisms still need to be clarified. Recently, there has been speculation that transmembrane pore formation is not the only mechanism of microbial killing. In fact several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented.
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              The expanding scope of antimicrobial peptide structures and their modes of action.

              Antimicrobial peptides (AMPs) are an integral part of the innate immune system that protect a host from invading pathogenic bacteria. To help overcome the problem of antimicrobial resistance, cationic AMPs are currently being considered as potential alternatives for antibiotics. Although extremely variable in length, amino acid composition and secondary structure, all peptides can adopt a distinct membrane-bound amphipathic conformation. Recent studies demonstrate that they achieve their antimicrobial activity by disrupting various key cellular processes. Some peptides can even use multiple mechanisms. Moreover, several intact proteins or protein fragments are now being shown to have inherent antimicrobial activity. A better understanding of the structure-activity relationships of AMPs is required to facilitate the rational design of novel antimicrobial agents. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                27 December 2016
                2016
                : 6
                : 194
                Affiliations
                [1] 1Promore Pharma AB, Karolinska Institutet Science Park Solna, Sweden
                [2] 2The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg Gothenburg, Sweden
                [3] 3SP Technical Research Institute of Sweden, Chemistry, Materials, and Surfaces Borås, Sweden
                Author notes

                Edited by: Matthew C. Wolfgang, University of North Carolina at Chapel Hill, USA

                Reviewed by: Charles Martin Dozois, Institut National de la Recherche Scientifique, Canada; Mathias Schmelcher, ETH Zurich, Switzerland

                *Correspondence: Margit Mahlapuu margit.mahlapuu@ 123456promorepharma.com
                Article
                10.3389/fcimb.2016.00194
                5186781
                28083516
                6ada2e4d-4fa4-45f4-9a49-78c6f3a407f6
                Copyright © 2016 Mahlapuu, Håkansson, Ringstad and Björn.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 October 2016
                : 12 December 2016
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 111, Pages: 12, Words: 9385
                Categories
                Microbiology
                Review

                Infectious disease & Microbiology
                amp,antimicrobial peptide,anti-infectives,antibiotic resistance,therapeutic agents

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