Research shows that plant pathogens reuse phage elements for bacterial warfare

Bacteriophages, viruses that attack and destroy bacteria, are ubiquitous in the natural world where they play a crucial role in regulating microbe populations in ways that are not yet well understood.

New research led by the University of Utah and University College London (UCL) has found that bacterial pathogens in plants can reuse elements of their own bacteriophages, or phages, to eradicate competing microbes.

These surprising findings suggest that such phage-derived elements could one day be exploited as an alternative to antibiotics, said Talia Karasov, an assistant professor at the U’s School of Biological Sciences. Titled “A phage tail-like bacteriocin suppresses competitors in metapopulations of pathogenic bacteria,” the study was published in Science.

This result was certainly not what she expected when she started this research with an international team of scientists.

Microbial pathogens are everywhere, but only a fraction of the time do they make people, other animals or plants sick, said Karasov, whose main research interest is in the interactions between plants and microbial pathogens. The Karasov laboratory seeks to understand the factors that lead to disease and epidemics, versus controlling the pathogens.

For previous research, the lab has looked at how a particular bacterial pathogen, Pseudomonas viridiflava, manifests in agricultural and wild environments. On cultivated land, they found, one variant would spread widely in a cropland and become the dominant microbe present. But that wasn’t the case on undeveloped land, prompting Karasov to find out why.

“We see that no single bacterial lineage can dominate. We wondered if the phages, the pathogens of our bacterial pathogens, could prevent individual strains from spreading – perhaps phages killed some strains and not others. That’s where our study began, but that is not where it ended,” Karasov said.

“We looked at the genomes of bacterial plant pathogens to see which phages were infecting them. But it wasn’t the phage we found that was interesting. The bacteria had taken a phage and repurposed it for warfare with other bacteria, and use these now to kill competing bacteria.”

According to her research, the pathogen acquires elements of the phages in the form of non-self-replicating clusters of recycled phages called tailocins, which penetrate the outer membranes of other pathogens and kill them.

After discovering this ongoing warfare in the populations of bacterial pathogens, the Karasov laboratory and Hernán Burbano’s laboratory at UCL mined the genomes of modern and historical pathogens to determine how the bacteria evolve to target each other.

“You can imagine an arms race between the bacteria, trying to kill each other and trying to develop resistance to each other over time,” Burbano said. “The herbarium samples from the past 200 years that we analyzed provided a glimpse into this arms race and insight into how bacteria avoid being killed by their competitors.”

Mining herbarium specimens for their microbial DNA

Burbano is a pioneer in the use of herbarium specimens to investigate the evolution of plants and their microbial pathogens. His laboratory maps the genomes of both host plants and those of the microbes associated with the plant at the time of collection more than a century ago.

For the phage study, Burbano analyzed historical specimens of Arabidopsis thaliana, a plant in the mustard family commonly called thale cress, collected in southwestern Germany, and compared them and the microbes they harbored with plants growing in the same part of Germany today.

“We found that all historical tailocins were present in our current dataset, suggesting that evolution has maintained the diversity of tailocin variants over the century scale,” he said. “This likely indicates a finite set of possible resistance/susceptibility mechanisms within our studied bacterial population.

Lead author Talia Backman wonders whether tailocins can help solve the looming crisis in antibiotic resistance seen in harmful bacteria that infect humans.

“We as a society are in urgent need of new antibiotics, and tailocins have potential as new antimicrobial treatments,” says Backman, a graduate student in the Karasov lab.

“Although tailocins have previously been found in other bacterial genomes and studied in laboratory settings, their impact and evolution in wild bacterial populations was not known. The fact that we discovered that these wild plant pathogens all have tailocins and that these tailocins evolve killing neighboring bacteria allows see how important they can be in nature.”

Like most pesticides, many of our antibiotics were developed decades ago to kill a wide range of harmful organisms, which are both harmful and beneficial to human and plant health. Tailocins, on the other hand, have greater specificity than most modern antibiotics and kill only a select few bacterial strains, suggesting they can be deployed without devastating entire biological communities.

“This is basic research at the moment, not yet ready for application, but I think there is good potential to adapt this for the treatment of infections,” Karasov said.

“We as a society have used uniform and broad-spectrum treatments in the treatment of both agricultural pests and bacterial pathogens in humans. The specificity of killing tailocin is one way you can imagine delivering more finely tailored treatments .”

Participating in the research with the U School of Biological Sciences were: University College London, the Max Planck Institute for Biology, the Complex Carbohydrate Research Center Analytical Services and Training Lab at the University of Georgia, New York University, the U’s Department of Biochemistry and Lawrence Berkeley National Laboratory.