Research reveals that plant pathogens reuse phage elements for bacterial combat

Bacteriophages, viruses that attack and destroy bacteria, are ubiquitous in the natural world, where they play essential roles in regulating microbial 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 plant bacterial pathogens are able to reuse elements of their own bacteriophages, or phages, to wipe out competing microbes.

These surprising findings suggest that such phage-derived elements could one day be used as an alternative to antibiotics, according to Talia Karasova, an assistant professor at the University of Biological Sciences. Study titled “Phage tail-like bacteriocin suppresses competitors in pathogenic bacterial metapopulations” Science.

This result was hardly what she expected to find when she embarked on this research with an international team of scientists.

Microbial pathogens are everywhere, but according to Karasov, whose primary research interest is interactions between plants and microbial pathogens, they only make people, other animals or plants sick a fraction of the time. Karasova’s lab seeks to understand the factors that lead to disease and epidemics versus keeping pathogens under control.

For its previous research, the lab looked at how a particular bacterial pathogen, Pseudomonas viridiflava, manifests itself in agricultural and wild settings. They found that in cultivated land, one variant would spread widely across the field and become the dominant microbe present. But that wasn’t the case with the uncultivated land, prompting Karasov to find out why.

“We see that no single lineage of bacteria can dominate. We wondered if phages, the pathogens of our bacterial pathogens, could prevent individual lineages from spreading—perhaps the phages were killing some strains and not others. That’s where our study started, but that’s not where it it’s over,” said Karasov.

“We looked into the genomes of plant bacterial pathogens to see which phages were infecting them. But it wasn’t the phage we found that was interesting. The bacteria took the phage and turned it into a war with other bacteria, now they use it to kill competing bacteria .”

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

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

“You can imagine an arms race between bacteria, where they try to kill each other and try to develop mutual resistance over time,” Burbano said. “The herbarium samples from the past 200 years that we analyzed provided a window into this arms race and provided 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 lab sequences the genomes of both host plants and the genomes of microbes associated with the plant at the time of collection more than a century ago.

For the phage research, Burbano analyzed historical specimens of Arabidopsis thaliana, a mustard plant commonly called watercress thalea, collected in southwestern Germany, comparing them and the microbes they harbored to plants growing in the same part of Germany today.

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

Lead author Talia Backman wonders whether tylocins could help solve the looming crisis of antibiotic resistance we’re seeing in harmful bacteria that infect humans.

“We as a society are in dire need of new antibiotics, and tailocins have potential as a new antimicrobial treatment,” said Backman, a graduate student in Karas’ lab.

“While tylocins have previously been found in other bacterial genomes and studied in the laboratory, their impact and evolution in wild bacterial populations was unknown. The fact that we found that all of these wild plant pathogens have tylocins and these tylocins are evolving.” killing neighboring bacteria shows how important they can be in nature.”

Like most pesticides, many of our antibiotics were developed decades ago to kill a wide variety of harmful organisms that are both harmful and beneficial to human and plant health. Tylocins, on the other hand, have greater specificity than most modern antibiotics, killing only a few select strains of bacteria, suggesting they could be deployed without wasting entire biological communities.

“At this point, it’s basic research that’s not ready for use yet, but I think there’s good potential that it could be adapted to treat infection,” Karasov said.

“We as a society have used uniform and broad-spectrum treatments in how we treat both agricultural pests and human bacterial pathogens. The specificity of killing with tylocin is a way you can imagine doing a more subtle treatment.”

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