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      Eradication of Vancomycin-Resistant Enterococci by Combining Phage and Vancomycin

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          Abstract

          Currently, effective options are needed to fight vancomycin-resistant Enterococcus faecalis (VRE). The present study shows that combinations of phage and vancomycin are highly efficient against VRE, despite being resistant to the antibiotic. Vancomycin-phage EFLK1 (anti- E. faecalis phage) synergy was assessed against VRE planktonic and biofilm cultures. The effect of the combined treatment on VRE biofilms was determined by evaluating the viable counts and biomass and then visualized using scanning electron microscopy (SEM). The cell wall peptidoglycan was stained after phage treatment, visualized by confocal microscopy and quantified by fluorescence activated cell sorting (FACS) analysis. The combined treatment was synergistically effective compared to treatment with phage or antibiotic alone, both in planktonic and biofilm cultures. Confocal microscopy and FACS analysis showed that fluorescence intensity of phage-treated bacteria increased eight-fold, suggesting a change in the peptidoglycan of the cell wall. Our results indicate that with combined treatment, VRE strains are not more problematic than sensitive strains and thus give hope in the continuous struggle against the current emergence of multidrug resistant pathogens.

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          Pros and cons of phage therapy.

          Many publications list advantages and disadvantages associated with phage therapy, which is the use of bacterial viruses to combat populations of nuisance or pathogenic bacteria. The goal of this commentary is to discuss many of those issues in a single location. In terms of "Pros," for example, phages can be bactericidal, can increase in number over the course of treatment, tend to only minimally disrupt normal flora, are equally effective against antibiotic-sensitive and antibiotic-resistant bacteria, often are easily discovered, seem to be capable of disrupting bacterial biofilms, and can have low inherent toxicities. In addition to these assets, we consider aspects of phage therapy that can contribute to its safety, economics, or convenience, but in ways that are perhaps less essential to the phage potential to combat bacteria. For example, autonomous phage transfer between animals during veterinary application could provide convenience or economic advantages by decreasing the need for repeated phage application, but is not necessarily crucial to therapeutic success. We also consider possible disadvantages to phage use as antibacterial agents. These "Cons," however, tend to be relatively minor.
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            Phage therapy: An alternative to antibiotics in the age of multi-drug resistance

            The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching.
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              Lysogeny in nature: mechanisms, impact and ecology of temperate phages.

              Viruses that infect bacteria (phages) can influence bacterial community dynamics, bacterial genome evolution and ecosystem biogeochemistry. These influences differ depending on whether phages establish lytic, chronic or lysogenic infections. Although the first two produce virion progeny, with lytic infections resulting in cell destruction, phages undergoing lysogenic infections replicate with cells without producing virions. The impacts of lysogeny are numerous and well-studied at the cellular level, but ecosystem-level consequences remain underexplored compared to those of lytic infections. Here, we review lysogeny from molecular mechanisms to ecological patterns to emerging approaches of investigation. Our goal is to highlight both its diversity and importance in complex communities. Altogether, using a combined viral ecology toolkit that is applied across broad model systems and environments will help us understand more of the diverse lifestyles and ecological impacts of lysogens in nature.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                16 October 2019
                October 2019
                : 11
                : 10
                : 954
                Affiliations
                [1 ]Department of Prosthodontics, Hadassah School of Dental Medicine, Hebrew University, Jerusalem 91120, Israel; mor.haramaty@ 123456gmail.com (M.S.); nuritb@ 123456ekmd.huji.ac.il (N.B.)
                [2 ]Faculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University, Jerusalem 91120, Israel; tinushy@ 123456yahoo.com (S.C.-G.); dnlgelman@ 123456gmail.com (D.G.)
                Author notes
                [* ]Correspondence: RonenH@ 123456ekmd.huji.ac.il
                [†]

                N.B. and R.H. contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-9967-730X
                Article
                viruses-11-00954
                10.3390/v11100954
                6833023
                31623253
                b0bafa5b-9e74-48e0-bfb3-eacebcc91252
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 August 2019
                : 11 October 2019
                Categories
                Article

                Microbiology & Virology
                phage therapy,enterococcus faecalis (vre),vancomycin,phage eflk1,phage-antibiotic synergy (pas)

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