Abstract
With the rise of antimicrobial resistance, novel ways to treat bacterial infections are required and the use of predatory bacteria may be one such approach. Bdellovibrio species have been shown in vitro to predate on a wide range of other Gram-negative bacteria, including CDC category A/B pathogens such as Yersinia pestis. The data reported here show that treatment of SKH-1 mice with Bdellovibrio bacteriovorus HD100 provided significant protection from a lethal challenge of Yersinia pestis CO92. This is the first report of protection conferred by predation in vivo against a systemic pathogen challenge. However, this protective effect was not observed in a preliminary study with Balb/c mice. Therefore the effects of the predatory bacteria are complex and may be dependent on immune status/genetics of the host. Overall, predatory bacteria may have utility as a therapeutic modality but further work is required to understand the predator-host interaction.
Highlights
Over recent decades, there has been a reduction in the rate of discovery of new antibiotics whilst there has been an increase in resistance to existing antibiotics, a situation that has spawned the term “antibiotic apocalypse”[1]
As Y. pestis has an intracellular phase during infection, we initially wished to determine whether B. bacteriovorus HD100 was able to survive in murine macrophages following phagocytosis
Whilst predator numbers reduced over time, predator could still be isolated from J774A.1 cells suggesting that B. bacteriovorus HD100:mCherry could enter macrophages and survive following phagocytosis (Fig. 1a)
Summary
There has been a reduction in the rate of discovery of new antibiotics whilst there has been an increase in resistance to existing antibiotics, a situation that has spawned the term “antibiotic apocalypse”[1]. Bdellovibrio enter the periplasmic space of the prey bacteria, replicate and lyse the prey to release progeny predator[2] One such approach to treating bacterial infections could be to use predatory bacteria such as Bdellovibrio as a ‘living’ antibiotic. There has been increasing research evaluating predatory bacteria in vitro for their ability to kill a range of Gram-negative bacteria from diverse genera, including multi-drug resistant clinical isolates[3,4]. In turn this has led to research into the efficacy of Bdellovibrio species to treat bacterial infections in vivo, as well as evaluation of the safety profile of administration of predatory bacteria. In this study, the ability of B. bacteriovorus HD100 to predate Y. pestis in vivo and potentially protect mice from a lethal challenge was investigated
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