title: Examining the safety of respiratory and intravenous inoculation of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus in a mouse model.
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.
authors.affiliation: Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Shatzkes
authors.affiliation: Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Chae
authors.affiliation: Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ 07103, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ 07103, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Ramirez
authors.affiliation: Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ 07103, USA.
authors.forename: Somdatta
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: 1] Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute, Rutgers New Jersey Medical School, Newark, NJ 07103, USA [2] Department of Biological Sciences, New York City College of Technology, Brooklyn, NY 11201, USA.
authors.forename: Liana
authors.initials: L
authors.lastname: Tsenova
authors.affiliation: Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Connell
authors.affiliation: Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ 07103, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kadouri
mesh_terms: D020561:Alphaproteobacteria / Q000254:growth & development*; D000818:Animals; D000898:Antibiosis / Q000502:physiology*; D001501:Bdellovibrio / Q000254:growth & development*; D018441:Biofilms / Q000254:growth & development; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D007275:Injections, Intravenous / Q000379:methods; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012137:Respiratory System / Q000378:metabolism / Q000382:microbiology*
chemical_list: D015850:Interleukin-6