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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 cell response to intravenous injection of B. bacteriovorus 109J.To profile the host cell response in the blood, mice were injected through the tail vein with B. bacteriovorus 109J. Profile of (A) total white blood cell (WBC) counts and (B) inflammatory cells after tail vein injection of B. bacteriovorus 109J. Blood was assessed at 3 and 18 hours post-injection. Blood profiles were performed by ANTECH Diagnostics (New Hyde Park, NY, USA). 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.
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f5: Inflammatory cell response to intravenous injection of B. bacteriovorus 109J.To profile the host cell response in the blood, mice were injected through the tail vein with B. bacteriovorus 109J. Profile of (A) total white blood cell (WBC) counts and (B) inflammatory cells after tail vein injection of B. bacteriovorus 109J. Blood was assessed at 3 and 18 hours post-injection. Blood profiles were performed by ANTECH Diagnostics (New Hyde Park, NY, USA). 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.

Mentions: To determine the effect of intravenous inoculation of predatory bacteria on host blood cell profile, 100 μl of blood was removed from each mouse at 3 and 18 hours post-exposure. White blood cell (WBC) counts were performed and the levels of individual cell types determined (Fig. 5). Surprisingly, total WBC counts decreased at 3 and 18 hours post-injection compared to the control. A 3.5- fold increase in the percentage of neutrophils in the blood was seen at 3 hours post-injection in mice inoculated with B. bacteriovorus 109J. However, the level of neutrophils in the blood returned to comparable levels seen in control animals by 18 hours post-exposure. In contrast, the percentage of monocytes in the blood remained elevated by 4.7-fold at 18 hours post-injection. Decreased percentages of lymphocytes in the blood were seen in conjunction with the observed increases of neutrophils and monocytes resulting from inoculation with predatory bacteria. Eosinophils were found at comparably low levels in both the control and treated mice.


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 cell response to intravenous injection of B. bacteriovorus 109J.To profile the host cell response in the blood, mice were injected through the tail vein with B. bacteriovorus 109J. Profile of (A) total white blood cell (WBC) counts and (B) inflammatory cells after tail vein injection of B. bacteriovorus 109J. Blood was assessed at 3 and 18 hours post-injection. Blood profiles were performed by ANTECH Diagnostics (New Hyde Park, NY, USA). 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.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Inflammatory cell response to intravenous injection of B. bacteriovorus 109J.To profile the host cell response in the blood, mice were injected through the tail vein with B. bacteriovorus 109J. Profile of (A) total white blood cell (WBC) counts and (B) inflammatory cells after tail vein injection of B. bacteriovorus 109J. Blood was assessed at 3 and 18 hours post-injection. Blood profiles were performed by ANTECH Diagnostics (New Hyde Park, NY, USA). 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.
Mentions: To determine the effect of intravenous inoculation of predatory bacteria on host blood cell profile, 100 μl of blood was removed from each mouse at 3 and 18 hours post-exposure. White blood cell (WBC) counts were performed and the levels of individual cell types determined (Fig. 5). Surprisingly, total WBC counts decreased at 3 and 18 hours post-injection compared to the control. A 3.5- fold increase in the percentage of neutrophils in the blood was seen at 3 hours post-injection in mice inoculated with B. bacteriovorus 109J. However, the level of neutrophils in the blood returned to comparable levels seen in control animals by 18 hours post-exposure. In contrast, the percentage of monocytes in the blood remained elevated by 4.7-fold at 18 hours post-injection. Decreased percentages of lymphocytes in the blood were seen in conjunction with the observed increases of neutrophils and monocytes resulting from inoculation with predatory bacteria. Eosinophils were found at comparably low levels in both the control and treated mice.

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