DARPA study finds cyanide-spitting bacteria

Scientists trying to understand how pathogenic bacteria protect themselves against antibiotics have found a bacterium that produces cyanide when under attack from a specific microbial predator.

Microbiologists in South Korea report in the journal mBio that the bacterium Chromobacterium piscinae produces cyanide when under attack from Bdellovibrio bacteriovorus HD100, a microbial predator found in rivers and soils that ingests its prey from the inside out. 

The researchers found that the prey produced levels of cyanide high enough to inhibit, but not kill, the B. bacteriovorus HD100.

Studying such mechanisms may lead scientists to better understand how antibiotic resistance occurs when bacteria change in ways that reduce the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections.  

Microbiologist and study leader Robert Mitchell, working at the Ulsan National Institute of Science and Technology in South Korea, is investigating how bacterial predators such as B. bacteriovorus HD100 might be developed as “living antibiotics” that can target bacterial pathogens.

The study suggests microbes may have means for resisting predation that only show up in certain environments. 

“Resistance may be present, but we’re not finding it because we’re not looking in the right conditions,” he says. “This study is kind of like a warning. To understand how germs may resist treatment, we need to look at the actual conditions in the host.”

Experiments showed that C. piscinae produced the protective cyanide in a nutrient-rich broth. In a medium devoid of nutrients, it didn’t produce it and was consumed. The researchers suspect that it likely uses some ingredient in the broth to catalyse production. That observation implies that a bacterium’s defences may depend on location – and, more generally, that bacteria may harbour protective mechanisms that are triggered in some environments but not in others.

These new findings align with work published earlier this year by Mitchell’s group, which identified compounds in human blood that inhibit predation of infectious bacterial strains such as E. coli and Salmonella enterica by B. bacteriovorus HD100.

In the previous study, Mitchell’s group noted B. bacteriovorus’ predatory nature and its propensity to attack and consume other bacterial strains, including some well-known pathogens. 

“This remarkable activity has been the focus of research for nearly five decades, with exciting practical applications to medical, agriculture and farming practices,” the study says.

When the researchers searched for clues for how C. piscinae resists predation, Mitchell says they didn’t expect to find cyanide. Their investigation began when, in earlier experiments, they noticed the bacterium survived attacks in nutrient-rich media. In a nutrient-poor environment, however, the predator ate the prey.

Ultimately, one of Mitchell’s students identified cyanide as the culprit. The researchers verified that C. piscinae produced large amounts of it when cultured in nutrient-rich broth, while those cultured in a nutrient-poor environment didn’t. Further experiments confirmed that cyanide inhibited B. bacteriovorus HD100. 

The cyanide didn’t poison the C. piscinae. “Some of the data in our study suggests the prey bacteria can degrade it,” Mitchell says.

The group now plans to look at how other predatory bacteria respond to cyanide, as well as other factors that can potentially inhibit or negatively impact predatory activity in microbes.

The mBio study was funded by a grant from the US Defence Advanced Research Projects Agency (DARPA), the research and development arm of the US Department of Defence. Mitchell notes that the findings and opinions of his research team should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office, DARPA, or the US Government.