Inner Workings: Probing predatory bacteria as an antibacterial remedy

Jyoti Madhusoodanan; PNAS November 12, 2019 116 (46) 22887-22890.

Figure: Researchers have started to evaluate predatory bacteria such as Bdellovibrio—shown here in a false-color transmission electron microscopy image at 50,000× magnification—as a means of treating intractable, antibiotic-resistant infections. Image credit: Science Source/ALFRED PASIEKA.

As microbiologists and public health officials scramble for weapons to combat antibiotic resistance, they may end up including an unlikely ally in their arsenal: other bacteria. The prime candidate right now is a predatory bacterium known as Bdellovibrio bacteriovorus.

Found in soils and water globally, B. bacteriovorus are free-living, harmless bacteria—harmless to humans, at least. In the microbial world, they’re voracious predators of gram-negative bacteria, a group that includes Salmonella, Escherichia coli, and several other pathogens. Bdellovibrio punch a hole in the membranes of their prey, enter and consume their contents, then burst out again to find their next meal. “They’re a very efficient killing machine,” says Daniel Kadouri, an associate professor at the Rutgers School of Dental Medicine in Newark, NJ. “They act kind of like the creature in the movie Alien.”

Researchers are now beginning to evaluate Bdellovibrio and other similar predatory bacteria as a route to treating intractable, antibiotic-resistant infections. They’re starting to learn how these predators work in different organs and against different pathogens. As they examine various infection scenarios, they are also discovering how these microbes work in concert with the native microbiome and immune cells.

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. “Regulatory agencies are starting to look at new therapies in ways that they didn’t need to before,” Kadouri says. “Suddenly people are studying phage[s], predatory bacteria, etc. These are things that don’t fit the guidelines for chemical drugs.”

But the rampant rise of antibiotic resistance means unconventional therapies should be explored, Kadouri adds. Rather than using single compounds, it’s time to treat infectious disease the way we treat cancer, he asserts—with a combination of immunotherapy, radiation therapy, chemotherapy, and more. “We got to this point because we looked at antibiotics as silver bullets, not recognizing that they produce huge amounts of selective pressure,” Kadouri says. “Now, the community needs to start building an arsenal beyond just antibiotics.

See https://www.pnas.org/content/116/46/22887