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      Are Phage Lytic Proteins the Secret Weapon To Kill Staphylococcus aureus?

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          ABSTRACT

          Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most threatening microorganisms for global human health. The current strategies to reduce the impact of S. aureus include a restrictive control of worldwide antibiotic use, prophylactic measures to hinder contamination, and the search for novel antimicrobials to treat human and animal infections caused by this bacterium. The last strategy is currently the focus of considerable research. In this regard, phage lytic proteins (endolysins and virion-associated peptidoglycan hydrolases [VAPGHs]) have been proposed as suitable candidates. Indeed, these proteins display narrow-spectrum antimicrobial activity and a virtual lack of bacterial-resistance development. Additionally, the therapeutic use of phage lytic proteins in S. aureus animal infection models is yielding promising results, showing good efficacy without apparent side effects. Nonetheless, human clinical trials are still in progress, and data are not available yet. This minireview also analyzes the main obstacles for introducing phage lytic proteins as human therapeutics against S. aureus infections. Besides the common technological problems derived from large-scale production of therapeutic proteins, a major setback is the lack of a proper legal framework regulating their use. In that sense, the relevant health authorities should urgently have a timely discussion about these new antimicrobials. On the other hand, the research community should provide data to dispel any doubts regarding their efficacy and safety. Overall, the appropriate scientific data and regulatory framework will encourage pharmaceutical companies to invest in these promising antimicrobials.

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          Stimuli-responsive nanocarriers for drug delivery.

          Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).
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            Restrictions on antimicrobial use in food animal production: an international regulatory and economic survey

            Background The administration of antimicrobial drugs to food animals at low doses for extended durations for growth promotion and disease prevention has been linked to the global health crisis of antimicrobial resistance. Internationally, multiple jurisdictions have responded by restricting antimicrobial use for these purposes, and by requiring a veterinary prescription to use these drugs in food animals. Opponents of these policies have argued that restrictions have been detrimental to food animal production where they have been adopted. Methods We surveyed the antimicrobial use policies of 17 political jurisdictions outside of the United States with respect to growth promotion, disease prevention, and veterinary oversight, and reviewed the available evidence regarding their production impacts, including measures of animal health. Jurisdictions were included if they were a top-five importer of a major U.S. food animal product in 2011, as differences between the policies of the U.S. and other jurisdictions may lead to trade barriers to U.S. food animal product exports. Jurisdictions were also included if information on their policies was publicly available in English. We searched the peer-reviewed and grey literatures and corresponded with jurisdictions’ U.S. embassies, regulators, and local experts. Results Jurisdictions were categorized by whether they prohibit use of antimicrobials for growth promotion and/or use of antimicrobials without a veterinary prescription. Of the 17 jurisdictions surveyed, six jurisdictions have prohibited both types of use, five jurisdictions have prohibited one use but not the other use, and five jurisdictions have not prohibited either use, while information was not available for one jurisdiction. Data on the production impacts of these prohibitions were limited, although available data, especially from Denmark and Sweden, suggest that restrictions on growth promotion use can be implemented with minimal production consequences. Conclusions A majority of leading U.S. trade partners have more stringent policies regarding antibiotic use and veterinary oversight in food animal production. Available data suggest that restrictions on growth promotion may not be detrimental to production in the long run, although additional research could be useful. There is evidence that discordance between the U.S. and other jurisdictions with respect to antimicrobial use in food animals may be detrimental to U.S. access to export markets for food animal products. The available economic evidence strengthens the rationale for restricting antimicrobial use in U.S. food animals.
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              Recombinant protein expression in Escherichia coli: advances and challenges

              Escherichia coli is one of the organisms of choice for the production of recombinant proteins. Its use as a cell factory is well-established and it has become the most popular expression platform. For this reason, there are many molecular tools and protocols at hand for the high-level production of heterologous proteins, such as a vast catalog of expression plasmids, a great number of engineered strains and many cultivation strategies. We review the different approaches for the synthesis of recombinant proteins in E. coli and discuss recent progress in this ever-growing field.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                mBio
                MBio
                mbio
                mbio
                mBio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                23 January 2018
                Jan-Feb 2018
                : 9
                : 1
                : e01923-17
                Affiliations
                [a ]Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, Spain
                Harvard Medical School
                Author notes
                Address correspondence to Pilar García, pgarcia@ 123456ipla.csic.es .
                Author information
                https://orcid.org/0000-0002-1577-9905
                Article
                mBio01923-17
                10.1128/mBio.01923-17
                5784253
                29362234
                1e57e9df-2105-4132-b5b9-64a7b72bf536
                Copyright © 2018 Gutiérrez et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 91, Pages: 17, Words: 10696
                Funding
                Funded by: Ministry of Science and Innovation Spain;
                Award ID: AGL2015-65673-R
                Award Recipient :
                Funded by: ERA-NET European Union;
                Award ID: BLAAT ID: 67
                Award Recipient :
                Funded by: Program of Science, Technology and Innovation Principado de Asturias;
                Award ID: GRUPIN14-139
                Award Recipient :
                Funded by: FEDER EU funds;
                Award ID: GRUPIN14-139
                Award Recipient :
                Categories
                Minireview
                Custom metadata
                January/February 2018

                Life sciences
                staphylococcus aureus,bacteriophage,bacteriophage therapy,endolysin
                Life sciences
                staphylococcus aureus, bacteriophage, bacteriophage therapy, endolysin

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