Exploring the Potential of Bacteriophages

Bacteriophages, viruses that target and destroy bacteria, are ubiquitous in the natural world. They play a crucial role in controlling microbe populations, though the mechanisms behind this regulation are not yet fully understood.

Recent studies conducted by the University of Utah and University College London (UCL) have discovered that plant bacterial pathogens can eliminate rival microorganisms by repurposing parts of their bacteriophages, or phages.

According to Talia Karasov, an Assistant Professor at the University of Utah's School of Biological Sciences, the unexpected results imply that these phage-derived components may one day be used as an antibiotic substitute.

When Karasov started this study with a global team of scientists, this outcome was by no means what Karasov had anticipated.

Although microbial pathogens are ubiquitous, Karasov, whose main area of interest is the interactions between plants and microbial pathogens, claims that only a small percentage of these pathogens cause illness in humans, other animals, or plants. In contrast to controlling pathogens, the Karasov lab aims to comprehend the causes of disease and epidemics.

In earlier work, the lab examined the symptoms of a specific bacterial pathogen, Pseudomonas viridiflava, in both agricultural and wild environments. The team discovered that on cultivated land, a particular variant would proliferate widely in a crop field and take over as the predominant microbe. However, that was not the case on uncultivated land, which led Karasov to investigate why.

We see that no single lineage of bacteria can dominate. We wondered whether the phages, the pathogens of our bacterial pathogens, could prevent single lineages from spreading – maybe phages were killing some strains and not others. That’s where our study started, but that’s not where it ended up. We looked in 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 had taken a phage and repurposed it for warfare with other bacteria, now using it to kill competing bacteria.”

Talia Karasov, Assistant Professor, School of Biological Sciences, University of Utah

The research, published in Science, indicates that the pathogen obtains phage components in the form of non-self-replicating tailocin clusters—repurposed phage clusters that pierce other pathogens' outer membranes and cause their death. Following the discovery of this continuous conflict within the populations of bacterial pathogens, the UCL laboratories of Hernán Burbano and Karasov mined the genomes of both extant and extinct pathogens to ascertain how the bacteria evolved to attack one another.

You can imagine an arms race between the bacteria where they’re trying to kill each other and trying to evolve resistance to one another over time. The herbarium samples from the past 200 years that we analyzed, provided a window into this arms race, providing insight into how bacteria evade being killed by their competitors.”

Hernán Burbano, University College London

Mining Herbarium Specimens for their Microbial DNA

The use of herbarium specimens to investigate the evolutionary history of plants and their microbial pathogens has been pioneered by Burbano. The microbes linked to the plant during its collection over a century ago and the host plants' genomes are sequenced in his lab.

To conduct the phage research, Burbano examined historical specimens of Arabidopsis thaliana, also known as thale cress, a plant from the mustard family collected in southwestern Germany. Burbano then compared the microbes these specimens harbored to plants currently growing in the same region of Germany.

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

Lead author Talia Backman ponders whether tailocins could be able to address the looming problem of antibiotic resistance in human-pathogenic bacteria.

We as a society are in dire need of new antibiotics, and tailocins have potential as new antimicrobial treatments. While tailocins have been found previously in other bacterial genomes, and have been studied in lab settings, their impact and evolution in wild bacterial populations was not known. The fact that we found that these wild plant pathogens all have tailocins and these tailocins are evolving to kill neighboring bacteria shows how significant they may be in nature.”

Talia Backman, Graduate Student and Lead Study Author, University of Utah

Many antibiotics, like most pesticides, were created decades ago to eradicate a wide range of dangerous organisms, including ones that are both detrimental and advantageous to plant and human health.

Conversely, tailocins exhibit higher specificity than most contemporary antibiotics. They selectively eliminate a limited number of bacterial strains, indicating that their use could be implemented without destroying entire biological communities.

Karasov said, “This is basic research at this point, not yet ready for application, but I think that there is good potential that this could be adapted for treating infection. We as a society have, in how we treat both pests in agriculture and bacterial pathogens in humans, used uniform and broad-spectrum treatments. The specificity of tailocin killing is a way that you could imagine doing more finely tailored treatments.”