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Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague

Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by the bacteria Yersinia pestis, is currently treated effectively with antibiotics. However, in the case of multidrug-resistant (MDR) bacteria, alternative treatments are required. Bact...

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Autores principales: Vagima, Yaron, Gur, David, Aftalion, Moshe, Moses, Sarit, Levy, Yinon, Makovitzki, Arik, Holtzman, Tzvi, Oren, Ziv, Segula, Yaniv, Fatelevich, Ella, Tidhar, Avital, Zauberman, Ayelet, Rotem, Shahar, Mamroud, Emanuelle, Steinberger-Levy, Ida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024586/
https://www.ncbi.nlm.nih.gov/pubmed/35458417
http://dx.doi.org/10.3390/v14040688
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author Vagima, Yaron
Gur, David
Aftalion, Moshe
Moses, Sarit
Levy, Yinon
Makovitzki, Arik
Holtzman, Tzvi
Oren, Ziv
Segula, Yaniv
Fatelevich, Ella
Tidhar, Avital
Zauberman, Ayelet
Rotem, Shahar
Mamroud, Emanuelle
Steinberger-Levy, Ida
author_facet Vagima, Yaron
Gur, David
Aftalion, Moshe
Moses, Sarit
Levy, Yinon
Makovitzki, Arik
Holtzman, Tzvi
Oren, Ziv
Segula, Yaniv
Fatelevich, Ella
Tidhar, Avital
Zauberman, Ayelet
Rotem, Shahar
Mamroud, Emanuelle
Steinberger-Levy, Ida
author_sort Vagima, Yaron
collection PubMed
description Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by the bacteria Yersinia pestis, is currently treated effectively with antibiotics. However, in the case of multidrug-resistant (MDR) bacteria, alternative treatments are required. Bacteriophage (phage) therapy has shown efficient antibacterial activity in various experimental animal models and in human patients infected with different MDR pathogens. Here, we evaluated the efficiency of фA1122 and PST phage therapy, alone or in combination with second-line antibiotics, using a well-established mouse model of pneumonic plague. Phage treatment significantly delayed mortality and limited bacterial proliferation in the lungs. However, the treatment did not prevent bacteremia, suggesting that phage efficiency may decrease in the circulation. Indeed, in vitro phage proliferation assays indicated that blood exerts inhibitory effects on lytic activity, which may be the major cause of treatment inefficiency. Combining phage therapy and second-line ceftriaxone treatment, which are individually insufficient, provided protection that led to the survival of all infected animals—a synergistic protective effect that represents a proof of concept for efficient combinatorial therapy in an emergency event of a plague outbreak involving MDR Y. pestis strains.
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spelling pubmed-90245862022-04-23 Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague Vagima, Yaron Gur, David Aftalion, Moshe Moses, Sarit Levy, Yinon Makovitzki, Arik Holtzman, Tzvi Oren, Ziv Segula, Yaniv Fatelevich, Ella Tidhar, Avital Zauberman, Ayelet Rotem, Shahar Mamroud, Emanuelle Steinberger-Levy, Ida Viruses Article Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by the bacteria Yersinia pestis, is currently treated effectively with antibiotics. However, in the case of multidrug-resistant (MDR) bacteria, alternative treatments are required. Bacteriophage (phage) therapy has shown efficient antibacterial activity in various experimental animal models and in human patients infected with different MDR pathogens. Here, we evaluated the efficiency of фA1122 and PST phage therapy, alone or in combination with second-line antibiotics, using a well-established mouse model of pneumonic plague. Phage treatment significantly delayed mortality and limited bacterial proliferation in the lungs. However, the treatment did not prevent bacteremia, suggesting that phage efficiency may decrease in the circulation. Indeed, in vitro phage proliferation assays indicated that blood exerts inhibitory effects on lytic activity, which may be the major cause of treatment inefficiency. Combining phage therapy and second-line ceftriaxone treatment, which are individually insufficient, provided protection that led to the survival of all infected animals—a synergistic protective effect that represents a proof of concept for efficient combinatorial therapy in an emergency event of a plague outbreak involving MDR Y. pestis strains. MDPI 2022-03-26 /pmc/articles/PMC9024586/ /pubmed/35458417 http://dx.doi.org/10.3390/v14040688 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vagima, Yaron
Gur, David
Aftalion, Moshe
Moses, Sarit
Levy, Yinon
Makovitzki, Arik
Holtzman, Tzvi
Oren, Ziv
Segula, Yaniv
Fatelevich, Ella
Tidhar, Avital
Zauberman, Ayelet
Rotem, Shahar
Mamroud, Emanuelle
Steinberger-Levy, Ida
Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague
title Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague
title_full Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague
title_fullStr Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague
title_full_unstemmed Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague
title_short Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague
title_sort phage therapy potentiates second-line antibiotic treatment against pneumonic plague
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024586/
https://www.ncbi.nlm.nih.gov/pubmed/35458417
http://dx.doi.org/10.3390/v14040688
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