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Expanding clinical phage microbiology: simulating phage inhalation for respiratory tract infections

Shira Ben Porat, Daniel Gelman, Ortal Yerushalmy, Sivan Alkalay-Oren, Shunit Coppenhagen-Glazer, Malena Cohen-Cymberknoh, Eitan Kerem, Israel Amirav, Ran Nir-Paz, Ronen Hazan
ERJ Open Research 2021; DOI: 10.1183/23120541.00367-2021
Shira Ben Porat
1Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
2Department of Military Medicine, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
7Equal contribution.
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Daniel Gelman
1Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
2Department of Military Medicine, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
3Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
7Equal contribution.
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Ortal Yerushalmy
1Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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Sivan Alkalay-Oren
1Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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Shunit Coppenhagen-Glazer
1Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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Malena Cohen-Cymberknoh
4Pediatric Pulmonology Unit and Cystic fibrosis Center, Hadassah Medical Center
5Faculty of Medicine, Hebrew University of Jerusalem, Israel
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Eitan Kerem
4Pediatric Pulmonology Unit and Cystic fibrosis Center, Hadassah Medical Center
5Faculty of Medicine, Hebrew University of Jerusalem, Israel
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Israel Amirav
6Pediatric Pulmonary Unit, Dana-Dwek Children's Hospital,
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Ran Nir-Paz
3Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
5Faculty of Medicine, Hebrew University of Jerusalem, Israel
8Equal contribution.
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Ronen Hazan
1Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
8Equal contribution.
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  • For correspondence: ronenh@ekmd.huji.ac.il
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Abstract

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation. Eight phages, most of which target cystic fibrosis (CF)-common pathogens, were aerosolized by jet nebulizer and administered to a real-scale computed tomography (CT)-derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.

Footnotes

This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.

Conflict of interests: The authors of "Simulating Phage Inhalation for Respiratory Tract Infections" by Ben Porat and Gelman et al. declare no conflict of interest.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received May 30, 2021.
  • Accepted August 4, 2021.
  • Copyright ©The authors 2021
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

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Expanding clinical phage microbiology: simulating phage inhalation for respiratory tract infections
Shira Ben Porat, Daniel Gelman, Ortal Yerushalmy, Sivan Alkalay-Oren, Shunit Coppenhagen-Glazer, Malena Cohen-Cymberknoh, Eitan Kerem, Israel Amirav, Ran Nir-Paz, Ronen Hazan
ERJ Open Research Jan 2021, 00367-2021; DOI: 10.1183/23120541.00367-2021

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Expanding clinical phage microbiology: simulating phage inhalation for respiratory tract infections
Shira Ben Porat, Daniel Gelman, Ortal Yerushalmy, Sivan Alkalay-Oren, Shunit Coppenhagen-Glazer, Malena Cohen-Cymberknoh, Eitan Kerem, Israel Amirav, Ran Nir-Paz, Ronen Hazan
ERJ Open Research Jan 2021, 00367-2021; DOI: 10.1183/23120541.00367-2021
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