Phage Therapy against <em>Staphylococcus aureus</em>: Selection and Optimization of Production Protocols of Novel Broad-Spectrum <em>Silviavirus</em> Phages

<b>Background:</b> Phage therapy a promising antimicrobial strategy to address antimicrobial resistance for infections caused by the major human pathogen <i>Staphylococcus aureus</i>. Development of therapeutic phages for human use should follow pharmaceutical standards, incl...

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Main Authors: Camille Kolenda, Mathieu Medina, Mélanie Bonhomme, Floriane Laumay, Tiphaine Roussel-Gaillard, Patricia Martins-Simoes, Anne Tristan, Fabrice Pirot, Tristan Ferry, Frédéric Laurent, PHAGEinLYON Study Group
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/9/1885
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author Camille Kolenda
Mathieu Medina
Mélanie Bonhomme
Floriane Laumay
Tiphaine Roussel-Gaillard
Patricia Martins-Simoes
Anne Tristan
Fabrice Pirot
Tristan Ferry
Frédéric Laurent
PHAGEinLYON Study Group
author_facet Camille Kolenda
Mathieu Medina
Mélanie Bonhomme
Floriane Laumay
Tiphaine Roussel-Gaillard
Patricia Martins-Simoes
Anne Tristan
Fabrice Pirot
Tristan Ferry
Frédéric Laurent
PHAGEinLYON Study Group
author_sort Camille Kolenda
collection DOAJ
description <b>Background:</b> Phage therapy a promising antimicrobial strategy to address antimicrobial resistance for infections caused by the major human pathogen <i>Staphylococcus aureus</i>. Development of therapeutic phages for human use should follow pharmaceutical standards, including selection of strictly lytic bacteriophages with high therapeutic potential and optimization of their production process. <b>Results:</b> Here, we describe three novel <i>Silviavirus</i> phages active against 82% of a large collection of strains (n = 150) representative of various methicillin-susceptible and -resistant <i>S. aureus</i> clones circulating worldwide. We also investigated the optimization of the efficiency and safety of phage amplification protocols. To do so, we selected a well-characterized bacterial strain in order to (i) maximize phage production yields, reaching phage titres of 10<sup>11</sup> PFU/mL in only 4 h; and (ii) facilitate phage purity while minimizing the risk of the presence of contaminants originating from the bacterial host; i.e., secreted virulence factors or induced temperate phages. <b>Conclusions:</b> In sum, we propose a quality-by-design approach for the amplification of broad-spectrum anti-<i>S. aureus</i> phages, facilitating the subsequent steps of the manufacturing process; namely, purification and quality control.
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spelling doaj.art-eac3100a97ee46eb8ad6c756383ddfc52023-11-23T18:22:22ZengMDPI AGPharmaceutics1999-49232022-09-01149188510.3390/pharmaceutics14091885Phage Therapy against <em>Staphylococcus aureus</em>: Selection and Optimization of Production Protocols of Novel Broad-Spectrum <em>Silviavirus</em> PhagesCamille Kolenda0Mathieu Medina1Mélanie Bonhomme2Floriane Laumay3Tiphaine Roussel-Gaillard4Patricia Martins-Simoes5Anne Tristan6Fabrice Pirot7Tristan Ferry8Frédéric Laurent9PHAGEinLYON Study GroupBacteriology Department, French National Reference Centre for Staphylococci, Institute for Infectious Agents, Hospices Civils de Lyon, 69004 Lyon, FranceBacteriology Department, French National Reference Centre for Staphylococci, Institute for Infectious Agents, Hospices Civils de Lyon, 69004 Lyon, FranceBacteriology Department, French National Reference Centre for Staphylococci, Institute for Infectious Agents, Hospices Civils de Lyon, 69004 Lyon, FranceBacteriology Department, French National Reference Centre for Staphylococci, Institute for Infectious Agents, Hospices Civils de Lyon, 69004 Lyon, FranceBacteriology Department, French National Reference Centre for Staphylococci, Institute for Infectious Agents, Hospices Civils de Lyon, 69004 Lyon, FranceBacteriology Department, French National Reference Centre for Staphylococci, Institute for Infectious Agents, Hospices Civils de Lyon, 69004 Lyon, FranceBacteriology Department, French National Reference Centre for Staphylococci, Institute for Infectious Agents, Hospices Civils de Lyon, 69004 Lyon, FrancePlateforme FRIPHARM, Service pharmaceutique, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, 69003 Lyon, FranceCIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, FranceBacteriology Department, French National Reference Centre for Staphylococci, Institute for Infectious Agents, Hospices Civils de Lyon, 69004 Lyon, France<b>Background:</b> Phage therapy a promising antimicrobial strategy to address antimicrobial resistance for infections caused by the major human pathogen <i>Staphylococcus aureus</i>. Development of therapeutic phages for human use should follow pharmaceutical standards, including selection of strictly lytic bacteriophages with high therapeutic potential and optimization of their production process. <b>Results:</b> Here, we describe three novel <i>Silviavirus</i> phages active against 82% of a large collection of strains (n = 150) representative of various methicillin-susceptible and -resistant <i>S. aureus</i> clones circulating worldwide. We also investigated the optimization of the efficiency and safety of phage amplification protocols. To do so, we selected a well-characterized bacterial strain in order to (i) maximize phage production yields, reaching phage titres of 10<sup>11</sup> PFU/mL in only 4 h; and (ii) facilitate phage purity while minimizing the risk of the presence of contaminants originating from the bacterial host; i.e., secreted virulence factors or induced temperate phages. <b>Conclusions:</b> In sum, we propose a quality-by-design approach for the amplification of broad-spectrum anti-<i>S. aureus</i> phages, facilitating the subsequent steps of the manufacturing process; namely, purification and quality control.https://www.mdpi.com/1999-4923/14/9/1885bacteriophagesphagesphage therapy<i>Staphylococcus</i>productionyield
spellingShingle Camille Kolenda
Mathieu Medina
Mélanie Bonhomme
Floriane Laumay
Tiphaine Roussel-Gaillard
Patricia Martins-Simoes
Anne Tristan
Fabrice Pirot
Tristan Ferry
Frédéric Laurent
PHAGEinLYON Study Group
Phage Therapy against <em>Staphylococcus aureus</em>: Selection and Optimization of Production Protocols of Novel Broad-Spectrum <em>Silviavirus</em> Phages
Pharmaceutics
bacteriophages
phages
phage therapy
<i>Staphylococcus</i>
production
yield
title Phage Therapy against <em>Staphylococcus aureus</em>: Selection and Optimization of Production Protocols of Novel Broad-Spectrum <em>Silviavirus</em> Phages
title_full Phage Therapy against <em>Staphylococcus aureus</em>: Selection and Optimization of Production Protocols of Novel Broad-Spectrum <em>Silviavirus</em> Phages
title_fullStr Phage Therapy against <em>Staphylococcus aureus</em>: Selection and Optimization of Production Protocols of Novel Broad-Spectrum <em>Silviavirus</em> Phages
title_full_unstemmed Phage Therapy against <em>Staphylococcus aureus</em>: Selection and Optimization of Production Protocols of Novel Broad-Spectrum <em>Silviavirus</em> Phages
title_short Phage Therapy against <em>Staphylococcus aureus</em>: Selection and Optimization of Production Protocols of Novel Broad-Spectrum <em>Silviavirus</em> Phages
title_sort phage therapy against em staphylococcus aureus em selection and optimization of production protocols of novel broad spectrum em silviavirus em phages
topic bacteriophages
phages
phage therapy
<i>Staphylococcus</i>
production
yield
url https://www.mdpi.com/1999-4923/14/9/1885
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