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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, View ORCID ProfileRonen Hazan
doi: https://doi.org/10.1101/2021.06.14.448272
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
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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
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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, Tel Aviv
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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
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Ronen Hazan
1Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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  • ORCID record for Ronen Hazan
  • 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 CF-common pathogens, were aerosolized and administered to a real-scale 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.

Take-Home Message Phage therapy can be used against infectious diseases if personally tailored. Using a 3D airways model, we show that phage delivery by inhalation to the respiratory tract is unpredictable and also requires a precise evaluation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 14, 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
bioRxiv 2021.06.14.448272; doi: https://doi.org/10.1101/2021.06.14.448272
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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
bioRxiv 2021.06.14.448272; doi: https://doi.org/10.1101/2021.06.14.448272

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