According to new research published in Science, many bacteria have acquired and repurposed viral sequence clusters that encode tail-like structures to kill competitors. At the University of Utah, researchers from the lab of Talia Karasov, PhD, demonstrated that different bacterial populations had evolved variants of these phage-derived elements, called tailocins, in concert with competitive populations. The researchers think that creating “tailocin cocktails” leveraging the genetic diversity of pathogens could mitigate resistance by concurrently targeting all the pathogen subpopulations in each of the hosts and environments (i.e., metapopulation).
Tails of war
Previous studies by Karasov’s group showed that a genetically diverse metapopulation of gram-negative Pseudomonas bacterial pathogens lived on the plant Arabidopsis thaliana in the wild. The prior results suggested that these pathogen populations do not undergo clonal expansions and that several co-occurring strains populate the plant, with no single strain becoming dominant. This led Karasov’s group to ask, What’s suppressing all of these Pseudomonas strains?
Karasov’s group first examined the many phage-homologous sequences in a wild Pseudomonas metapopulation to see if they were linked to turnover in the Pseudomonas that infects Arabidopsis thaliana plants. Of the 1524 Pseudomonas genomes collected from A. thaliana in southwestern Germany, more than 85% are classified as a specific clade of P. viridiflava that colonizes A. thaliana throughout Europe and the U.S.
They found viral sequences in 99.3% of the genomes, with an average of two viral sequences per genome. The most abundant viral cluster encodes a phage remnant resembling a phage tail called a tailocin or repurposed phage tail. Each pathogenic Pseudomonas strain has a different type of tailocin that targets a different type of lipopolysaccharide in the outer membrane of other pathogenic Pseudomonas strains that are present.
By looking at historical samples dating back 200 years, the University of Utah researchers showed that the same tail fiber and lipopolysaccharide variants have been maintained in the Pseudomonas populations for the past 200 years. This is important because bacteria are capable of rapid adaptation. Still, the fact that a defined set of variants was maintained in these populations indicates selective constraints on the evolution of this system, consistent with what has been found in viral evolution. The vital evolutionary conservation and correlation between loci suggest that inter-Pseudomonas strain competition through the tailocin is a strong and persistent selective pressure on Pseudomonas pathogens.
A possible alternative to small-molecule antibiotics
With any antimicrobial treatment, there is a risk that the target bacterium will evolve resistance. Tailocin therapy, like phage therapy, has been proposed as an alternative to small-molecule antibiotics. In animal and plant models, tailocins have been shown to inhibit targeted pathogens effectively.
The results of this study show that by looking at the genetic diversity of tailocins in a group of pathogens, it is possible to find “tailocin cocktails” that can work against a certain set of resistance mechanisms. These cocktails can simultaneously target the metapopulation, which reduces the probability of resistance evolution.
In the future, studying and analyzing the tailocin repertoire from various wild Pseudomonas populations will reveal potential connections between the tail fiber and lipopolysaccharide composition. It will also provide insights into the time frames in which tailocin resistance develops in natural environments.
