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      Antimicrobial peptides: Application informed by evolution

      1 , 2 , 3 , 4

      Science

      American Association for the Advancement of Science (AAAS)

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          Abstract

          Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.

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          Most cited references 76

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          Antibiotic resistance-the need for global solutions.

          The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

            Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.
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              Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes.

              Mosquitoes are vectors of parasitic and viral diseases of immense importance for public health. The acquisition of the genome sequence of the yellow fever and Dengue vector, Aedes aegypti (Aa), has enabled a comparative phylogenomic analysis of the insect immune repertoire: in Aa, the malaria vector Anopheles gambiae (Ag), and the fruit fly Drosophila melanogaster (Dm). Analysis of immune signaling pathways and response modules reveals both conservative and rapidly evolving features associated with different functional gene categories and particular aspects of immune reactions. These dynamics reflect in part continuous readjustment between accommodation and rejection of pathogens and suggest how innate immunity may have evolved.
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                Author and article information

                Journal
                Science
                Science
                American Association for the Advancement of Science (AAAS)
                0036-8075
                1095-9203
                April 30 2020
                May 01 2020
                April 30 2020
                May 01 2020
                : 368
                : 6490
                : eaau5480
                Affiliations
                [1 ]Department of Entomology, Cornell Institute of Host-Microbe Interactions and Disease, Cornell University, Ithaca, NY, USA.
                [2 ]MedStar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC, USA.
                [3 ]Freie Universität Berlin, Evolutionary Biology, Institut für Biologie, Königin-Luise-Strasse 1-3, 14195 Berlin, Germany.
                [4 ]Berlin-Brandenburg Institute of Advanced Biodiversity Research (BBIB), 14195 Berlin, Germany.
                Article
                10.1126/science.aau5480
                © 2020

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