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.
Highlights
Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are Gram-negative proteobacteria that are obligate predators of other Gram-negative bacteria[1, 2]
In response to the alarming rise of antibiotic-resistant infections, scientists have begun to explore new ways to treat bacterial infections; one of these approaches is the use of predatory bacteria[15]
We demonstrated the ability of predatory bacteria to attenuate bacterial burden in vivo within the lungs of rats[19]
Summary
Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are Gram-negative proteobacteria that are obligate predators of other Gram-negative bacteria[1, 2]. Injections of predatory bacteria were shown to cooperate with host immune cells to treat Shigella infection in the hindbrains of zebrafish larvae, leading to increased zebrafish survival[20]. It is still unknown if predatory bacteria can reduce pathogen burden introduced into an animal through other modes of administration, including directly into the bloodstream. This is of interest as a potential alternative to treat MDR-infections, and as a potential therapeutic for sepsis triggered by Gram-negative pathogens. The work presented here further addresses concerns with the idea of developing predatory bacteria into a novel antimicrobial
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