Examining the efficacy of intravenous administration of predatory bacteria in rats

Abstract The proteobacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are obligate predators of Gram-negative bacteria, and have been proposed to be used to treat multidrug-resistant bacterial infections. The ability of predatory bacteria to reduce bacterial burden in vivo within the...

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Autores principales: Kenneth Shatzkes, Eric Singleton, Chi Tang, Michael Zuena, Sean Shukla, Shilpi Gupta, Sonal Dharani, Joseph Rinaggio, Daniel E. Kadouri, Nancy D. Connell
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/ea5ad5bb28b041fa8cdc648bb0ff5f25
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spelling oai:doaj.org-article:ea5ad5bb28b041fa8cdc648bb0ff5f252021-12-02T15:06:19ZExamining the efficacy of intravenous administration of predatory bacteria in rats10.1038/s41598-017-02041-32045-2322https://doaj.org/article/ea5ad5bb28b041fa8cdc648bb0ff5f252017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02041-3https://doaj.org/toc/2045-2322Abstract The proteobacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are obligate predators of Gram-negative bacteria, and have been proposed to be used to treat multidrug-resistant bacterial infections. The ability of predatory bacteria to reduce bacterial burden in vivo within the lungs of rats has been demonstrated, but it was unknown if predatory bacteria can attenuate systemic bacterial burden administered intravenously. In this study, we first assessed the safety of intravenous inoculation of predatory bacteria in rats. No rat morbidity or adverse histopathology of various organs due to predatory bacteria administration was observed. An increase in proinflammatory cytokines (TNFα and KC/GRO) was observed at two hours post-inoculation; however, cytokines returned to baseline levels by 18 hours. Furthermore, bacterial dissemination analysis demonstrated that predatory bacteria were efficiently cleared from the host by 20 days post-injection. To determine whether predatory bacteria could reduce bacterial burden in vivo, Klebsiella pneumoniae was injected into the tail veins of rats and followed with multiple doses of predatory bacteria over 16 or 24 hours. Predatory bacteria were unable to significantly reduce K. pneumoniae burden in the blood or prevent dissemination to other organs. The results suggest that predatory bacteria may not be effective for treatment of acute blood infections.Kenneth ShatzkesEric SingletonChi TangMichael ZuenaSean ShuklaShilpi GuptaSonal DharaniJoseph RinaggioDaniel E. KadouriNancy D. ConnellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kenneth Shatzkes
Eric Singleton
Chi Tang
Michael Zuena
Sean Shukla
Shilpi Gupta
Sonal Dharani
Joseph Rinaggio
Daniel E. Kadouri
Nancy D. Connell
Examining the efficacy of intravenous administration of predatory bacteria in rats
description Abstract The proteobacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are obligate predators of Gram-negative bacteria, and have been proposed to be used to treat multidrug-resistant bacterial infections. The ability of predatory bacteria to reduce bacterial burden in vivo within the lungs of rats has been demonstrated, but it was unknown if predatory bacteria can attenuate systemic bacterial burden administered intravenously. In this study, we first assessed the safety of intravenous inoculation of predatory bacteria in rats. No rat morbidity or adverse histopathology of various organs due to predatory bacteria administration was observed. An increase in proinflammatory cytokines (TNFα and KC/GRO) was observed at two hours post-inoculation; however, cytokines returned to baseline levels by 18 hours. Furthermore, bacterial dissemination analysis demonstrated that predatory bacteria were efficiently cleared from the host by 20 days post-injection. To determine whether predatory bacteria could reduce bacterial burden in vivo, Klebsiella pneumoniae was injected into the tail veins of rats and followed with multiple doses of predatory bacteria over 16 or 24 hours. Predatory bacteria were unable to significantly reduce K. pneumoniae burden in the blood or prevent dissemination to other organs. The results suggest that predatory bacteria may not be effective for treatment of acute blood infections.
format article
author Kenneth Shatzkes
Eric Singleton
Chi Tang
Michael Zuena
Sean Shukla
Shilpi Gupta
Sonal Dharani
Joseph Rinaggio
Daniel E. Kadouri
Nancy D. Connell
author_facet Kenneth Shatzkes
Eric Singleton
Chi Tang
Michael Zuena
Sean Shukla
Shilpi Gupta
Sonal Dharani
Joseph Rinaggio
Daniel E. Kadouri
Nancy D. Connell
author_sort Kenneth Shatzkes
title Examining the efficacy of intravenous administration of predatory bacteria in rats
title_short Examining the efficacy of intravenous administration of predatory bacteria in rats
title_full Examining the efficacy of intravenous administration of predatory bacteria in rats
title_fullStr Examining the efficacy of intravenous administration of predatory bacteria in rats
title_full_unstemmed Examining the efficacy of intravenous administration of predatory bacteria in rats
title_sort examining the efficacy of intravenous administration of predatory bacteria in rats
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/ea5ad5bb28b041fa8cdc648bb0ff5f25
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