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      Characterization of novel recombinant mycobacteriophages derived from homologous recombination between two temperate phages

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          Abstract

          Comparative analyses of mycobacteriophage genomes reveals extensive genetic diversity in genome organization and gene content, contributing to widespread mosaicism. We previously reported that the prophage of mycobacteriophage Butters (cluster N) provides defense against infection by Island3 (subcluster I1). To explore the anti-Island3 defense mechanism, we attempted to isolate Island3 defense escape mutants on a Butters lysogen, but only uncovered phages with recombinant genomes comprised of regions of Butters and Island3 arranged from left arm to right arm as Butters-Island3-Butters (BIBs). Recombination occurs within two distinct homologous regions that encompass lysin A, lysin B, and holin genes in one segment, and RecE and RecT genes in the other. Structural genes of mosaic BIB genomes are contributed by Butters while the immunity cassette is derived from Island3. Consequently, BIBs are morphologically identical to Butters (as shown by transmission electron microscopy) but are homoimmune with Island3. Recombinant phages overcome antiphage defense and silencing of the lytic cycle. We leverage this observation to propose a stratagem to generate novel phages for potential therapeutic use.

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          Abstract

          In silico comparative analysis of mycobacteriophage genomes reveals extensive genetic diversity and widespread genome mosaicism. Mohammed et al., describe a novel mosaic recombinant phage named BIB (Butters-Island3-Butters) produced in situ by homologous recombination between the Mycobacteriophage Butters (cluster N) prophage within a lysogen and the invading Island3 (subcluster I1) genome. Mycobacteriophage Butters prophage-encoded factors block lytic infection of heterotypic Mycobacteriophage Island3 but the recombinant BIB genome contains genetic modules that allow escape from prophage-mediated defense and repressor-mediated lytic repression.

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          Most cited references47

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          NIH Image to ImageJ: 25 years of image analysis

          For the past twenty five years the NIH family of imaging software, NIH Image and ImageJ have been pioneers as open tools for scientific image analysis. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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            Jalview Version 2—a multiple sequence alignment editor and analysis workbench

            Summary: Jalview Version 2 is a system for interactive WYSIWYG editing, analysis and annotation of multiple sequence alignments. Core features include keyboard and mouse-based editing, multiple views and alignment overviews, and linked structure display with Jmol. Jalview 2 is available in two forms: a lightweight Java applet for use in web applications, and a powerful desktop application that employs web services for sequence alignment, secondary structure prediction and the retrieval of alignments, sequences, annotation and structures from public databases and any DAS 1.53 compliant sequence or annotation server. Availability: The Jalview 2 Desktop application and JalviewLite applet are made freely available under the GPL, and can be downloaded from www.jalview.org Contact: g.j.barton@dundee.ac.uk
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              Bacteriophage resistance mechanisms.

              Phages are now acknowledged as the most abundant microorganisms on the planet and are also possibly the most diversified. This diversity is mostly driven by their dynamic adaptation when facing selective pressure such as phage resistance mechanisms, which are widespread in bacterial hosts. When infecting bacterial cells, phages face a range of antiviral mechanisms, and they have evolved multiple tactics to avoid, circumvent or subvert these mechanisms in order to thrive in most environments. In this Review, we highlight the most important antiviral mechanisms of bacteria as well as the counter-attacks used by phages to evade these systems.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                G3 (Bethesda)
                Genetics
                g3journal
                G3: Genes|Genomes|Genetics
                Oxford University Press (US )
                2160-1836
                December 2023
                15 September 2023
                15 September 2023
                : 13
                : 12
                : jkad210
                Affiliations
                Department of Biological Sciences, Lehigh University , Bethlehem, PA 18015, USA
                Memsel, Inc. , 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA
                Department of Biological Sciences, Lehigh University , Bethlehem, PA 18015, USA
                Biotechnology and Bioengineering Department , Sandia National Laboratories, Livermore, CA 94551, USA
                Department of Biological Sciences, Lehigh University , Bethlehem, PA 18015, USA
                New York Institute of Technology College of Osteopathic Medicine , 101 Northern Blvd., Glen Head, NY 11545, USA
                Department of Biological Sciences, Lehigh University , Bethlehem, PA 18015, USA
                Department of Biological Sciences, Lehigh University , Bethlehem, PA 18015, USA
                Author notes
                Corresponding author: Department of Biological Sciences, Lehigh University, 111 Research Drive, B217 Iacocca Hall, Bethlehem, PA 18015, USA. Email: vcw0@ 123456lehigh.edu

                Conflicts of interest The author(s) declare no conflict of interest.

                Article
                jkad210
                10.1093/g3journal/jkad210
                10700106
                37713616
                4b261af2-b604-4688-8ab5-aa24dcb12368
                © The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 August 2023
                : 31 August 2023
                : 17 October 2023
                Page count
                Pages: 10
                Funding
                Funded by: Lehigh University, DOI 10.13039/100008234;
                Funded by: Pennsylvania Department of Community and Economic Development, DOI 10.13039/100004905;
                Award ID: PITA C000063030 PA DCED
                Funded by: Lehigh University Presidential fellowship;
                Funded by: Nemes fellowship;
                Funded by: Nemes fellowship;
                Categories
                Investigation
                AcademicSubjects/SCI01180
                AcademicSubjects/SCI01140
                Featured

                Genetics
                mycobacteriophage genomics,phage genome mosaicism,homologous recombination,phage genetic diversity,bacteriophage evolution,phage therapy

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