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A compassionate study showed the clinical improvement of a CF patient with a disseminated M. abscessus (GD01) infection, following injection of a phage cocktail, including phage Muddy. Broadening the use of phage therapy in patients as a potential antibacterial alternative necessitates the development of biological models to improve the reliability and successful prediction of phage therapy in the clinic. Herein, we demonstrate that Muddy very efficiently lyses GD01 in vitro, an effect substantially increased with standard drugs. Remarkably, this cooperative activity was retained in an M. abscessus model of infection in CFTR-depleted zebrafish, associated with a striking increase in larval survival and reduction in pathological signs. The activity of Muddy was lost in macrophage-ablated larvae, suggesting that successful phage therapy relies on functional innate immunity. CFTR-depleted zebrafish represent a practical model to rapidly assess phage treatment efficacy against M. abscessus isolates, allowing the identification of drug combinations accompanying phage therapy and treatment prediction in patients.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.049159","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T17:57:06Z","timestamp":1631815026000},"source":"Crossref","is-referenced-by-count":55,"title":["Mycobacteriophage\u2013antibiotic therapy promotes enhanced clearance of drug-resistant\n                    <i>Mycobacterium abscessus<\/i>"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5553-5270","authenticated-orcid":false,"given":"Matt D.","family":"Johansen","sequence":"first","affiliation":[{"name":"Institut de Recherche en Infectiologie de Montpellier, Centre National de la Recherche Scientifique UMR 9004, Universit\u00e9 de Montpellier, Montpellier 34293, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matth\u00e9o","family":"Alcaraz","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Infectiologie de Montpellier, Centre National de la Recherche Scientifique UMR 9004, Universit\u00e9 de Montpellier, Montpellier 34293, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3666-711X","authenticated-orcid":false,"given":"Rebekah M.","family":"Dedrick","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2636-3734","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Roquet-Ban\u00e8res","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Infectiologie de Montpellier, Centre National de la Recherche Scientifique UMR 9004, Universit\u00e9 de Montpellier, Montpellier 34293, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Hamela","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Infectiologie de Montpellier, Centre National de la Recherche Scientifique UMR 9004, Universit\u00e9 de Montpellier, Montpellier 34293, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6705-6821","authenticated-orcid":false,"given":"Graham F.","family":"Hatfull","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-4458","authenticated-orcid":false,"given":"Laurent","family":"Kremer","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Infectiologie de Montpellier, Centre National de la Recherche Scientifique UMR 9004, Universit\u00e9 de Montpellier, Montpellier 34293, France"},{"name":"INSERM, Institut de Recherche en Infectiologie de Montpellier, Montpellier 34293, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"2021091621570249400_DMM049159C1","doi-asserted-by":"publisher","first-page":"2726","DOI":"10.1099\/ijsem.0.002011","article-title":"Reinstating Mycobacterium massiliense and Mycobacterium bolletii as species of the Mycobacterium abscessus complex","volume":"67","author":"Adekambi","year":"2017","journal-title":"Int. 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