All about ‘Bdellovibrio bacteriovorus’: a bacteria-eating bacteria for antibiotic resistance

• The key healthcare application of predatory bacteria would be to treat ailments in which multi drug resistant (MDR) organisms are the etiologic agents.
• Predatory bacteria have also shown the ability to control the overgrowth of MDR bacteria in vitro from the genera Acinetobacter, Escherichia, Klebsiella and Pseudomonas.
• The usage of bacterial predators as anti-periodontitis agents in vivo is a grey area as of now because their aerobic lifestyle (Rotem et al., 2014) .
• An investigation which evaluated multiple BALOs for their predation capacity on a panel of periodontitis pathogens revealed that B. bacteriovorus HD100 had the highest versatility as it was capable of preying upon four of the six pathogens i.e Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Eikenella corrodens (E. corrodens), Fusobacterium nucleatum (F. nucleatum) and Prevotella intermedia (P. intermedia).
• Biofilms have also been reported as susceptible to predatory bacteria attack in vitro.

Efficacy to control infection

Two recent studies have assessed the ability of predatory bacteria to be developed into novel antimicrobial agent as they were able to control a Gram-negative infection in vivo. Importantly, the authors were able to use live cell imaging to determine that predation occurred in vivo and that the predators cooperate with native host immune cells to first decrease bacterial burden, before being cleared from the host by neutrophils and macrophages.

• Predatory bacteria treatment potentially could be effective for infections occurring at immune privileged sites, such as the urinary tract, as the predators could persist longer with less immune elements in their direct environment.
• The wide spectrum of activity demonstrated by bacterial predators coupled with their non- toxic nature and their secreted proteases against human cells suggested that direct topical application on wounds is a direction worth exploring.
• Finally, the fact that predatory bacteria have little effect overall on the gut microbial diversity compares well against antibiotics. In fact, there is evidence that predatory bacteria may contribute to health by serving as an ecological balancer in normal gut flora, as B. bacteriovorus has been found in lower abundances in patients with chronic diseases of the gut compared with healthy individuals.

Resistance to predation?

A significant advantage over current antibiotics is that development of predation resistance in a normally susceptible bacterial species has yet to be confirmed. Shemesh and Jurkevitch demonstrated that some bacterial cells can develop a transient, plastic resistance to predation; so it was hypothesized that although the prey might evolve in order to avoid predation, the predator, being a live microorganism, might differentiate quickly to counter any emerging resistance, a potential advantage not possessed by current antibiotics.

However, in high concentrations, the metabolite indole produced by E coli and other bacteria, blocks and prevents the predatory bacteria from attacking altogether, which may be considered as a limitation of the predatory action. Future research about other such metabolites should be considered.

Potentially safe applications

Bacterial predators could be effective antibacterial agents and fears pertaining safety can be cast aside as experimental results suggest that predators do not induce a sustained immune response and are rapidly cleared from mammalian hosts.

• Globally, bacterial keratitis is one of the most common causes for irreversible blindness. The usage of contact lens predisposes individuals to bacterial infection, particularly by Gram- negative organisms. An investigation showed the efficacy of bacterial predators to kill keratitis isolates ofP. aeruginosa and Serratia marcescens (S. marcescens).
• Bacterial predators could potentially be used to address infections due to Helicobacter pylori (H. pylori), a group 1 carcinogen because multiple strains of Bdellovibrio demonstrated predation capacity against the said pathogen in both viable and viable but nonculturable conditions.
• The safety data pertaining use of bacterial predators for gastrointestinal ailments is limited.

A Post-antibiotic Future

Even a single dose of Bdellovibrio directed toward a local infection is a long way off. Their broad-ranging, nonspecific activities seemingly have both pros and cons.

Bdellovibrio could consume beneficial microflora in areas other than the gut. Preliminary studies by Connell, Kadouri , and Sockett have found mixed effects. Using live bacteria as antibacterial therapy also poses manufacturing and regulatory challenges. Because Bdellovibrio grows only on other bacteria and carries its own LPS—a molecule that’s currently used as a marker of contamination in drug manufacture—new standards will have to be created for predatory bacteria–based remedies.

But the rise of antibiotic resistance means unconventional therapies should be explored. Rather than using single compounds, it’s time to treat infectious disease the way we treat cancer with a combination of immunotherapy, radiation therapy, chemotherapy, and more. The community needs to start building an arsenal beyond just antibiotics.

Conclusion

The issue of AMR needs to be addressed and bacterial predators offer a potential path forward. The present findings showed that predatory bacteria demonstrate impressive activity in vitro against multiple pathogens but these results are not necessarily indicative of in vivo efficacy. Combination therapy should be the preferred for the use as bacterial predators appear to function better as an ancillary therapy, yet monotherapy could be suitable in specific conditions. Bacterial predators are only effective against Gram-negative organisms .Therefore, efficacy on other Gram-positive organisms and intracellular organisms should be assessed. The safety data pertaining usage of predatory bacteria in vivo is limited in some areas, hence more research needs to be done to address the gaps.

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