Predatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs

ABSTRACT Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are predatory bacteria that naturally—and obligately—prey on other Gram-negative bacteria, and their use has been proposed as a potential new approach to control microbial infection. The ability of predatory bacteria to prey on Gram-...

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Autores principales:	Kenneth Shatzkes, Eric Singleton, Chi Tang, Michael Zuena, Sean Shukla, Shilpi Gupta, Sonal Dharani, Onoyom Onyile, Joseph Rinaggio, Nancy D. Connell, Daniel E. Kadouri
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1520c071c52e46d7b47840db11de2067
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spelling	oai:doaj.org-article:1520c071c52e46d7b47840db11de20672021-11-15T15:50:14ZPredatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs10.1128/mBio.01847-162150-7511https://doaj.org/article/1520c071c52e46d7b47840db11de20672016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01847-16https://doaj.org/toc/2150-7511ABSTRACT Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are predatory bacteria that naturally—and obligately—prey on other Gram-negative bacteria, and their use has been proposed as a potential new approach to control microbial infection. The ability of predatory bacteria to prey on Gram-negative human pathogens in vitro is well documented; however, the in vivo safety and efficacy of predatory bacteria have yet to be fully assessed. In this study, we examined whether predatory bacteria can reduce bacterial burden in the lungs in an in vivo mammalian system. Initial safety studies were performed by intranasal inoculation of rats with predatory bacteria. No adverse effects or lung pathology were observed in rats exposed to high concentrations of predatory bacteria at up to 10 days postinoculation. Enzyme-linked immunosorbent assay (ELISA) of the immune response revealed a slight increase in inflammatory cytokine levels at 1 h postinoculation that was not sustained by 48 h. Additionally, dissemination experiments showed that predators were efficiently cleared from the host by 10 days postinoculation. To measure the ability of predatory bacteria to reduce microbial burden in vivo, we introduced sublethal concentrations of Klebsiella pneumoniae into the lungs of rats via intranasal inoculation and followed with multiple doses of predatory bacteria over 24 h. Predatory bacteria were able to reduce K. pneumoniae bacterial burden, on average, by more than 3.0 log10 in the lungs of most rats as measured by CFU plating. The work presented here provides further support for the idea of developing predatory bacteria as a novel biocontrol agent. IMPORTANCE A widely held notion is that antibiotics are the greatest medical advance of the last 50 years. However, the rise of multidrug-resistant (MDR) bacterial infections has become a global health crisis over the last decade. As we enter the postantibiotic era, it is crucial that we begin to develop new strategies to combat bacterial infection. Here, we report one such new approach: the use of predatory bacteria (Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus) that naturally—and obligately—prey on other Gram-negative bacteria. To our knowledge, this is the first study that demonstrated the ability of predatory bacteria to attenuate the bacterial burden of a key human pathogen in an in vivo mammalian system. As the prevalence of MDR infections continues to rise each year, our results may represent a shift in how we approach treating microbial infections in the future.Kenneth ShatzkesEric SingletonChi TangMichael ZuenaSean ShuklaShilpi GuptaSonal DharaniOnoyom OnyileJoseph RinaggioNancy D. ConnellDaniel E. KadouriAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Kenneth Shatzkes Eric Singleton Chi Tang Michael Zuena Sean Shukla Shilpi Gupta Sonal Dharani Onoyom Onyile Joseph Rinaggio Nancy D. Connell Daniel E. Kadouri Predatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs
description	ABSTRACT Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are predatory bacteria that naturally—and obligately—prey on other Gram-negative bacteria, and their use has been proposed as a potential new approach to control microbial infection. The ability of predatory bacteria to prey on Gram-negative human pathogens in vitro is well documented; however, the in vivo safety and efficacy of predatory bacteria have yet to be fully assessed. In this study, we examined whether predatory bacteria can reduce bacterial burden in the lungs in an in vivo mammalian system. Initial safety studies were performed by intranasal inoculation of rats with predatory bacteria. No adverse effects or lung pathology were observed in rats exposed to high concentrations of predatory bacteria at up to 10 days postinoculation. Enzyme-linked immunosorbent assay (ELISA) of the immune response revealed a slight increase in inflammatory cytokine levels at 1 h postinoculation that was not sustained by 48 h. Additionally, dissemination experiments showed that predators were efficiently cleared from the host by 10 days postinoculation. To measure the ability of predatory bacteria to reduce microbial burden in vivo, we introduced sublethal concentrations of Klebsiella pneumoniae into the lungs of rats via intranasal inoculation and followed with multiple doses of predatory bacteria over 24 h. Predatory bacteria were able to reduce K. pneumoniae bacterial burden, on average, by more than 3.0 log10 in the lungs of most rats as measured by CFU plating. The work presented here provides further support for the idea of developing predatory bacteria as a novel biocontrol agent. IMPORTANCE A widely held notion is that antibiotics are the greatest medical advance of the last 50 years. However, the rise of multidrug-resistant (MDR) bacterial infections has become a global health crisis over the last decade. As we enter the postantibiotic era, it is crucial that we begin to develop new strategies to combat bacterial infection. Here, we report one such new approach: the use of predatory bacteria (Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus) that naturally—and obligately—prey on other Gram-negative bacteria. To our knowledge, this is the first study that demonstrated the ability of predatory bacteria to attenuate the bacterial burden of a key human pathogen in an in vivo mammalian system. As the prevalence of MDR infections continues to rise each year, our results may represent a shift in how we approach treating microbial infections in the future.
format	article
author	Kenneth Shatzkes Eric Singleton Chi Tang Michael Zuena Sean Shukla Shilpi Gupta Sonal Dharani Onoyom Onyile Joseph Rinaggio Nancy D. Connell Daniel E. Kadouri
author_facet	Kenneth Shatzkes Eric Singleton Chi Tang Michael Zuena Sean Shukla Shilpi Gupta Sonal Dharani Onoyom Onyile Joseph Rinaggio Nancy D. Connell Daniel E. Kadouri
author_sort	Kenneth Shatzkes
title	Predatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs
title_short	Predatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs
title_full	Predatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs
title_fullStr	Predatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs
title_full_unstemmed	Predatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs
title_sort	predatory bacteria attenuate <named-content content-type="genus-species">klebsiella pneumoniae</named-content> burden in rat lungs
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/1520c071c52e46d7b47840db11de2067
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Predatory Bacteria Attenuate <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Burden in Rat Lungs

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