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Examining the safety of respiratory and intravenous inoculation of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus in a mouse model.

Shatzkes K, Chae R, Tang C, Ramirez GC, Mukherjee S, Tsenova L, Connell ND, Kadouri DE - Sci Rep (2015)

Bottom Line: We found no reduction in mouse viability after intranasal or intravenous inoculation of B. bacteriovorus 109J, HD100 or M. aeruginosavorus.Intravenous injection caused an increase of IL-6 in the kidney and spleen, TNF in the liver and CXCL-1/KC in the blood at 3 hours post-exposure, returning to baseline levels by 18 hours.Furthermore, qPCR detected predators were cleared from the host quickly and efficiently.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.

ABSTRACT
Bdellovibrio spp. and Micavibrio spp. are Gram-negative predators that feed on other Gram-negative bacteria, making predatory bacteria potential alternatives to antibiotics for treating multi-drug resistant infections. While the ability of predatory bacteria to control bacterial infections in vitro is well documented, the in vivo effect of predators on a living host has yet to be extensively examined. In this study, respiratory and intravenous inoculations were used to determine the effects of predatory bacteria in mice. We found no reduction in mouse viability after intranasal or intravenous inoculation of B. bacteriovorus 109J, HD100 or M. aeruginosavorus. Introducing predators into the respiratory tract of mice provoked a modest inflammatory response at 1 hour post-exposure, but was not sustained at 24 hours, as measured by RT-qPCR and ELISA. Intravenous injection caused an increase of IL-6 in the kidney and spleen, TNF in the liver and CXCL-1/KC in the blood at 3 hours post-exposure, returning to baseline levels by 18 hours. Histological analysis of tissues showed no pathological changes due to predatory bacteria. Furthermore, qPCR detected predators were cleared from the host quickly and efficiently. This work addresses some of the safety concerns regarding the potential use of predatory bacteria as a live antibiotic.

No MeSH data available.


Related in: MedlinePlus

Inflammatory cytokine profile in response to intravenous injection of B. bacteriovorus 109J.(A–C) qPCR analysis of IL-6, IL-12, IFNγ, and TNF in response to tail vein injection of B. bacteriovorus 109J relative to PBS control. Expression of cytokines was assessed in the (A) kidney, (B) liver and (C) spleen at 3 and 18 hours post-injection. Fold induction was calculated using the ΔΔCt by approximation method using an endogenous calibrator (β-actin). Five mice per treatment group were used at each time point. Data represent mean ± standard deviation. (D) ELISA analysis of IL-1β, IL-6, IL-10, IL-12, CXCL-1/KC, IFNγ, and TNF in response to tail vein injection of B. bacteriovorus 109J relative to PBS control. Inflammatory proteins were assessed in the blood at 3 and 18 hours post-injection. Five mice per treatment group were used at each time point. Data represent mean ± standard error of the mean. Student’s t-test was performed to compare each treated sample to their respective control sample, *P < 0.05; **P < 0.01; ***P < 0.001.
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f6: Inflammatory cytokine profile in response to intravenous injection of B. bacteriovorus 109J.(A–C) qPCR analysis of IL-6, IL-12, IFNγ, and TNF in response to tail vein injection of B. bacteriovorus 109J relative to PBS control. Expression of cytokines was assessed in the (A) kidney, (B) liver and (C) spleen at 3 and 18 hours post-injection. Fold induction was calculated using the ΔΔCt by approximation method using an endogenous calibrator (β-actin). Five mice per treatment group were used at each time point. Data represent mean ± standard deviation. (D) ELISA analysis of IL-1β, IL-6, IL-10, IL-12, CXCL-1/KC, IFNγ, and TNF in response to tail vein injection of B. bacteriovorus 109J relative to PBS control. Inflammatory proteins were assessed in the blood at 3 and 18 hours post-injection. Five mice per treatment group were used at each time point. Data represent mean ± standard error of the mean. Student’s t-test was performed to compare each treated sample to their respective control sample, *P < 0.05; **P < 0.01; ***P < 0.001.

Mentions: To examine the effects of intravenous introduction of predatory bacteria on the host immune system, we injected 1 × 108 PFU/mouse of B. bacteriovorus 109J into the tail vein of mice (5 mice per treatment group). Mice were visually monitored for signs of illness or discomfort, and euthanized at either 3, 18 hours or 20 days post-injection, when organs and blood were harvested. To model a multiple bacteremia event, a group of mice were re-injected with 1 × 108 PFU/mouse of B. bacteriovorus 109J at 10 days post- initial injection. The kidney, liver and spleen were harvested to measure inflammatory cytokines (Fig. 6).


Examining the safety of respiratory and intravenous inoculation of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus in a mouse model.

Shatzkes K, Chae R, Tang C, Ramirez GC, Mukherjee S, Tsenova L, Connell ND, Kadouri DE - Sci Rep (2015)

Inflammatory cytokine profile in response to intravenous injection of B. bacteriovorus 109J.(A–C) qPCR analysis of IL-6, IL-12, IFNγ, and TNF in response to tail vein injection of B. bacteriovorus 109J relative to PBS control. Expression of cytokines was assessed in the (A) kidney, (B) liver and (C) spleen at 3 and 18 hours post-injection. Fold induction was calculated using the ΔΔCt by approximation method using an endogenous calibrator (β-actin). Five mice per treatment group were used at each time point. Data represent mean ± standard deviation. (D) ELISA analysis of IL-1β, IL-6, IL-10, IL-12, CXCL-1/KC, IFNγ, and TNF in response to tail vein injection of B. bacteriovorus 109J relative to PBS control. Inflammatory proteins were assessed in the blood at 3 and 18 hours post-injection. Five mice per treatment group were used at each time point. Data represent mean ± standard error of the mean. Student’s t-test was performed to compare each treated sample to their respective control sample, *P < 0.05; **P < 0.01; ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528228&req=5

f6: Inflammatory cytokine profile in response to intravenous injection of B. bacteriovorus 109J.(A–C) qPCR analysis of IL-6, IL-12, IFNγ, and TNF in response to tail vein injection of B. bacteriovorus 109J relative to PBS control. Expression of cytokines was assessed in the (A) kidney, (B) liver and (C) spleen at 3 and 18 hours post-injection. Fold induction was calculated using the ΔΔCt by approximation method using an endogenous calibrator (β-actin). Five mice per treatment group were used at each time point. Data represent mean ± standard deviation. (D) ELISA analysis of IL-1β, IL-6, IL-10, IL-12, CXCL-1/KC, IFNγ, and TNF in response to tail vein injection of B. bacteriovorus 109J relative to PBS control. Inflammatory proteins were assessed in the blood at 3 and 18 hours post-injection. Five mice per treatment group were used at each time point. Data represent mean ± standard error of the mean. Student’s t-test was performed to compare each treated sample to their respective control sample, *P < 0.05; **P < 0.01; ***P < 0.001.
Mentions: To examine the effects of intravenous introduction of predatory bacteria on the host immune system, we injected 1 × 108 PFU/mouse of B. bacteriovorus 109J into the tail vein of mice (5 mice per treatment group). Mice were visually monitored for signs of illness or discomfort, and euthanized at either 3, 18 hours or 20 days post-injection, when organs and blood were harvested. To model a multiple bacteremia event, a group of mice were re-injected with 1 × 108 PFU/mouse of B. bacteriovorus 109J at 10 days post- initial injection. The kidney, liver and spleen were harvested to measure inflammatory cytokines (Fig. 6).

Bottom Line: We found no reduction in mouse viability after intranasal or intravenous inoculation of B. bacteriovorus 109J, HD100 or M. aeruginosavorus.Intravenous injection caused an increase of IL-6 in the kidney and spleen, TNF in the liver and CXCL-1/KC in the blood at 3 hours post-exposure, returning to baseline levels by 18 hours.Furthermore, qPCR detected predators were cleared from the host quickly and efficiently.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.

ABSTRACT
Bdellovibrio spp. and Micavibrio spp. are Gram-negative predators that feed on other Gram-negative bacteria, making predatory bacteria potential alternatives to antibiotics for treating multi-drug resistant infections. While the ability of predatory bacteria to control bacterial infections in vitro is well documented, the in vivo effect of predators on a living host has yet to be extensively examined. In this study, respiratory and intravenous inoculations were used to determine the effects of predatory bacteria in mice. We found no reduction in mouse viability after intranasal or intravenous inoculation of B. bacteriovorus 109J, HD100 or M. aeruginosavorus. Introducing predators into the respiratory tract of mice provoked a modest inflammatory response at 1 hour post-exposure, but was not sustained at 24 hours, as measured by RT-qPCR and ELISA. Intravenous injection caused an increase of IL-6 in the kidney and spleen, TNF in the liver and CXCL-1/KC in the blood at 3 hours post-exposure, returning to baseline levels by 18 hours. Histological analysis of tissues showed no pathological changes due to predatory bacteria. Furthermore, qPCR detected predators were cleared from the host quickly and efficiently. This work addresses some of the safety concerns regarding the potential use of predatory bacteria as a live antibiotic.

No MeSH data available.


Related in: MedlinePlus