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      Mycobacteriophages: From Petri dish to patient

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      Author(s): * ,
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      Publication date (Electronic):
      Journal: PLoS Pathogens
      Publisher: Public Library of Science

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mycobacteriophages—bacteriophages infecting Mycobacterium hosts—contribute substantially to our understanding of viral diversity and evolution, provide resources for advancing Mycobacterium genetics, are the basis of high-impact science education programs, and show considerable therapeutic potential. Over 10,000 individual mycobacteriophages have been isolated by high school and undergraduate students using the model organism Mycobacterium smegmatis mc 2155 and 2,100 have been completely sequenced, giving a high-resolution view of the phages that infect a single common host strain. The phage genomes are revealed to be highly diverse and architecturally mosaic and are replete with genes of unknown function. Mycobacteriophages have provided many widely used tools for Mycobacterium genetics including integration-proficient vectors and recombineering systems, as well as systems for efficient delivery of reporter genes, transposons, and allelic exchange substrates. The genomic insights and engineering tools have facilitated exploration of phages for treatment of Mycobacterium infections, although their full therapeutic potential has yet to be realized.

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          Most cited references130

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          One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.

          K. Datsenko, B Wanner (2000)
          We have developed a simple and highly efficient method to disrupt chromosomal genes in Escherichia coli in which PCR primers provide the homology to the targeted gene(s). In this procedure, recombination requires the phage lambda Red recombinase, which is synthesized under the control of an inducible promoter on an easily curable, low copy number plasmid. To demonstrate the utility of this approach, we generated PCR products by using primers with 36- to 50-nt extensions that are homologous to regions adjacent to the gene to be inactivated and template plasmids carrying antibiotic resistance genes that are flanked by FRT (FLP recognition target) sites. By using the respective PCR products, we made 13 different disruptions of chromosomal genes. Mutants of the arcB, cyaA, lacZYA, ompR-envZ, phnR, pstB, pstCA, pstS, pstSCAB-phoU, recA, and torSTRCAD genes or operons were isolated as antibiotic-resistant colonies after the introduction into bacteria carrying a Red expression plasmid of synthetic (PCR-generated) DNA. The resistance genes were then eliminated by using a helper plasmid encoding the FLP recombinase which is also easily curable. This procedure should be widely useful, especially in genome analysis of E. coli and other bacteria because the procedure can be done in wild-type cells.
          Article 0 comments Cited 1842 times – based on 0 reviews     Review now
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            Genes required for mycobacterial growth defined by high density mutagenesis.

            Christopher Sassetti, Dana Boyd, Eric Rubin (2003)
            Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we describe the use of transposon site hybridization (TraSH) to comprehensively identify the genes required by the causative agent, Mycobacterium tuberculosis, for optimal growth. These genes include those that can be assigned to essential pathways as well as many of unknown function. The genes important for the growth of M. tuberculosis are largely conserved in the degenerate genome of the leprosy bacillus, Mycobacterium leprae, indicating that non-essential functions have been selectively lost since this bacterium diverged from other mycobacteria. In contrast, a surprisingly high proportion of these genes lack identifiable orthologues in other bacteria, suggesting that the minimal gene set required for survival varies greatly between organisms with different evolutionary histories.
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              Engineered bacteriophages for treatment of a patient with a disseminated drug resistant Mycobacterium abscessus

              Rebekah M. Dedrick, Carlos Guerrero-Bustamante, Rebecca Garlena … (2019)
              A 15-year-old cystic fibrosis patient with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules.
              Article 0 comments Cited 457 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Antje Blumenthal: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS Pathog
                Journal ID (iso-abbrev): PLoS Pathog
                Journal ID (publisher-id): plos
                Title: PLoS Pathogens
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Print): 1553-7366
                ISSN (Electronic): 1553-7374
                Publication date (Electronic): 7 July 2022
                Publication date Collection: July 2022
                Volume: 18
                Issue: 7
                Electronic Location Identifier: e1010602
                Affiliations
                [001] Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America
                University of Queensland, AUSTRALIA
                Author notes

                I have read the journal’s policy and have the following conflicts: I receive research support from Janssen Pharmaceuticals, and am a consultant for Tessera Inc. and Janssen.

                Author information
                https://orcid.org/0000-0002-6705-6821
                Article
                Publisher ID: PPATHOGENS-D-22-00601
                DOI: 10.1371/journal.ppat.1010602
                PMC ID: 9262239
                PubMed ID: 35797343
                SO-VID: 98ba0a01-4037-4bdb-becb-44c8a0ff2612
                Copyright © © 2022 Graham F. Hatfull
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Page count
                Figures: 4, Tables: 0, Pages: 25
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: GM131729
                Award Recipient :
                ORCID: https://orcid.org/0000-0002-6705-6821
                Funded by: funder-id http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Award ID: GT12053
                Award Recipient :
                ORCID: https://orcid.org/0000-0002-6705-6821
                This work was supported by grants from the National Institutes of Health grant GM131729 (GFH) and the Howard Hughes Medical Institute Grant GT12053 (GFH). The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Review
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Bacteriophages
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Bacteria
                Subject: Actinobacteria
                Subject: Mycobacterium Tuberculosis
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Bacteria
                Subject: Actinobacteria
                Subject: Mycobacteria
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Bacterial Pathogens
                Subject: Mycobacteria
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Bacterial Pathogens
                Subject: Mycobacteria
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: Genomics
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: Genomics
                Subject: Microbial Genomics
                Subject: Viral Genomics
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Microbial Genomics
                Subject: Viral Genomics
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Virology
                Subject: Viral Genomics
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immunity
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immunity
                Subject: Biology and life sciences
                Subject: Genetics
                Subject: DNA
                Subject: DNA recombination
                Subject: Biology and life sciences
                Subject: Biochemistry
                Subject: Nucleic acids
                Subject: DNA
                Subject: DNA recombination
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Virology
                Subject: Viral Replication
                Subject: Lysogeny

                ScienceOpen disciplines: Infectious disease & Microbiology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology

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