{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:08:18Z","timestamp":1790820498077,"version":"4.1.0"},"reference-count":87,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Phage-derived therapies comprise phage therapy and the use of phage-derived proteins as anti-bacterial therapy. Bacteriophages are natural viruses that target specific bacteria. They were proposed to be used to treat bacterial infections in the 1920s, before the discovery and widespread over-commercialized use of antibiotics. Phage therapy was totally abandoned in Western countries, whereas it is still used in Poland, Georgia and Russia. We review here the history of phage therapy by focusing on bone and joint infection, and on the development of phage therapy in France in this indication. We discuss the rationale of its use in bacterial infection and show the feasibility of phage therapy in the 2020s, based on several patients with complex bone and joint infection who recently received phages as compassionate therapy. Although the status of phage therapy remains to be clarified by health care authorities, obtaining pharmaceutical-grade therapeutic phages (i.e., following good manufacturing practice guidelines or being \u201cGMP-like\u201d) targeting bacterial species of concern is essential. Moreover, multidisciplinary clinical expertise has to determine what could be the relevant indications to perform clinical trials. Finally \u201cphage therapy 2.0\u201d has to integrate the following steps: (i) follow the status of phage therapy, that is not settled and defined; (ii) develop in each country a close relationship with the national health care authority; (iii) develop industrial\u2013academic partnerships; (iv) create academic reference centers; (v) identify relevant clinical indications; (vi) use GMP\/GMP-like phages with guaranteed quality bioproduction; (vii) start as salvage therapy; (vii) combine with antibiotics and adequate surgery; and (viii) perform clinical trials, to finally (ix) demonstrate in which clinical settings phage therapy provides benefit. Phage-derived proteins such as peptidoglycan hydrolases, polysaccharide depolymerases or lysins are enzymes that also have anti-biofilm activity. In contrast to phages, their development has to follow the classical process of medicinal products. Phage therapy and phage-derived products also have a huge potential to treat biofilm-associated bacterial diseases, and this is of crucial importance in the worldwide spread of antimicrobial resistance.<\/jats:p>","DOI":"10.3390\/v13122414","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T03:21:05Z","timestamp":1638847265000},"page":"2414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Past and Future of Phage Therapy and Phage-Derived Proteins in Patients with Bone and Joint Infection"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3082-7001","authenticated-orcid":false,"given":"Tristan","family":"Ferry","sequence":"first","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Villeurbanne, France"},{"name":"Centre de R\u00e9f\u00e9rences des IOA Complexes de Lyon, CRIOAc Lyon, 69004 Lyon, France"},{"name":"StaPath Team, Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Kolenda","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Villeurbanne, France"},{"name":"Centre de R\u00e9f\u00e9rences des IOA Complexes de Lyon, CRIOAc Lyon, 69004 Lyon, France"},{"name":"StaPath Team, Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4693-4605","authenticated-orcid":false,"given":"Thomas","family":"Briot","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubin","family":"Souche","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Villeurbanne, France"},{"name":"Centre de R\u00e9f\u00e9rences des IOA Complexes de Lyon, CRIOAc Lyon, 69004 Lyon, France"},{"name":"StaPath Team, Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Lustig","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Villeurbanne, France"},{"name":"Centre de R\u00e9f\u00e9rences des IOA Complexes de Lyon, CRIOAc Lyon, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6780-9646","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Josse","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Villeurbanne, France"},{"name":"Centre de R\u00e9f\u00e9rences des IOA Complexes de Lyon, CRIOAc Lyon, 69004 Lyon, France"},{"name":"StaPath Team, Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Batailler","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Villeurbanne, France"},{"name":"Centre de R\u00e9f\u00e9rences des IOA Complexes de Lyon, CRIOAc Lyon, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Pirot","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Villeurbanne, France"},{"name":"Laboratoire de Recherche et D\u00e9veloppement de Pharmacie Gal\u00e9nique Industrielle, Facult\u00e9 de Pharmacie, EA 4169 \u201cFonctions Physiologiques et Pathologiques de la Barri\u00e8re Cutan\u00e9e\u201d, Universit\u00e9 Claude-Bernard Lyon 1, 8, Avenue Rockefeller, CEDEX 08, 69373 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Medina","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Leboucher","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Laurent","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, 69004 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Villeurbanne, France"},{"name":"Centre de R\u00e9f\u00e9rences des IOA Complexes de Lyon, CRIOAc Lyon, 69004 Lyon, France"},{"name":"StaPath Team, Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Lyon BJI Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the PHAGEinLYON Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ref_1","first-page":"49","article-title":"Phagoth\u00e9rapie pour les patients pr\u00e9sentant une infection osteoarticulaire: Historique, fondements, faisabilit\u00e9 et perspectives en France","volume":"24","author":"Ferry","year":"2020","journal-title":"Virologie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1146\/annurev.micro.55.1.437","article-title":"Bacteriophage Therapy","volume":"55","author":"Summers","year":"2001","journal-title":"Annu. 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