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      Learning from Bacteriophages - Advantages and Limitations of Phage and Phage-Encoded Protein Applications

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          Abstract

          The emergence of bacteria resistance to most of the currently available antibiotics has become a critical therapeutic problem. The bacteria causing both hospital and community-acquired infections are most often multidrug resistant. In view of the alarming level of antibiotic resistance between bacterial species and difficulties with treatment, alternative or supportive antibacterial cure has to be developed. The presented review focuses on the major characteristics of bacteriophages and phage-encoded proteins affecting their usefulness as antimicrobial agents. We discuss several issues such as mode of action, pharmacodynamics, pharmacokinetics, resistance and manufacturing aspects of bacteriophages and phage-encoded proteins application.

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          Most cited references279

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          Dispersing biofilms with engineered enzymatic bacteriophage.

          Synthetic biology involves the engineering of biological organisms by using modular and generalizable designs with the ultimate goal of developing useful solutions to real-world problems. One such problem involves bacterial biofilms, which are crucial in the pathogenesis of many clinically important infections and are difficult to eradicate because they exhibit resistance to antimicrobial treatments and removal by host immune systems. To address this issue, we engineered bacteriophage to express a biofilm-degrading enzyme during infection to simultaneously attack the bacterial cells in the biofilm and the biofilm matrix, which is composed of extracellular polymeric substances. We show that the efficacy of biofilm removal by this two-pronged enzymatic bacteriophage strategy is significantly greater than that of nonenzymatic bacteriophage treatment. Our engineered enzymatic phage substantially reduced bacterial biofilm cell counts by approximately 4.5 orders of magnitude ( approximately 99.997% removal), which was about two orders of magnitude better than that of nonenzymatic phage. This work demonstrates the feasibility and benefits of using engineered enzymatic bacteriophage to reduce bacterial biofilms and the applicability of synthetic biology to an important medical and industrial problem.
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            5500 Phages examined in the electron microscope.

            "Phages" include viruses of eubacteria and archaea. At least 5568 phages have been examined in the electron microscope since the introduction of negative staining in 1959. Most virions (96%) are tailed. Only 208 phages (3.7%) are polyhedral, filamentous, or pleomorphic. Phages belong to one order, 17 families, and three "floating" groups. Phages are found in 11 eubacterial and archaeal phyla and infect 154 host genera, mostly of the phyla Actinobacteria, Firmicutes, and Proteobacteria. Of the tailed phages, 61% have long, noncontractile tails and belong to the family Siphoviridae. Convergent evolution is visible in the morphology of certain phage groups.
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              The phage-host arms race: shaping the evolution of microbes.

              Bacteria, the most abundant organisms on the planet, are outnumbered by a factor of 10 to 1 by phages that infect them. Faced with the rapid evolution and turnover of phage particles, bacteria have evolved various mechanisms to evade phage infection and killing, leading to an evolutionary arms race. The extensive co-evolution of both phage and host has resulted in considerable diversity on the part of both bacterial and phage defensive and offensive strategies. Here, we discuss the unique and common features of phage resistance mechanisms and their role in global biodiversity. The commonalities between defense mechanisms suggest avenues for the discovery of novel forms of these mechanisms based on their evolutionary traits.
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                Author and article information

                Journal
                Curr Protein Pept Sci
                Curr. Protein Pept. Sci
                CPPS
                Current Protein & Peptide Science
                Bentham Science Publishers
                1389-2037
                1875-5550
                December 2012
                December 2012
                : 13
                : 8
                : 699-722
                Affiliations
                [1 ]Institute of Genetics and Microbiology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wrocław, Poland
                [2 ]Laboratory of Gene Technology, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, box 2462, B-3001 Leuven, Belgium
                Author notes
                [* ]Address correspondence to this author at the Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland; Tel:/Fax: +48 71 325 21 51; Email: zuzanna.drulis-kawa@ 123456microb.uni.wroc.pl
                Article
                CPPS-13-699
                10.2174/138920312804871193
                3594737
                23305359
                70274b09-b0c9-4682-8dd1-57aec87396e2
                © 2012 Bentham Science Publishers

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 June 2012
                : 12 July 2012
                : 20 September 2012
                Categories
                Article

                Biochemistry
                antibiotics,bacterial multidrug resistance,bacteriophage therapy,phage-encoded proteins application,

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