A new study from scientists at New York University, Yale University, and elsewhere has demonstrated that several phage species can coexist stably on a genetically uniform strain of E. coli. They believe that a better understanding of how these viruses coexist could lead to new phage-based treatments for bacterial infections, including strains that have become resistant to antibiotics.
Full details of the study are published in Science in a paper titled, “Diverse phage communities are maintained stably on a clonal bacterial host.”
In it, the researchers report isolating and analyzing E. coli phages from different environmental samples. They found that despite competition between viruses, different phage species preferred slower or faster growing cells that randomly appeared in the E. coli population. This preference allowed each phage species to find and survive in their own niche on the same host. For example, two species of phage, labeled N and S, co-existed because N survived better in fast-growing bacterial cells, while phage S did better with slow-growing cells.
“Our study contributes to the burgeoning field of studying the social lives of viruses,” said Nora Pyenson, PhD, a postdoctoral scholar at NYU Langone Health and first author on the study. “We often think of viruses purely in terms of their impact on the host, but they also exist in the context of other viral species. These phage communities show how diversity emerges even among the simplest bits of biology.”
The study also tests an assumption that the genetic diversity of bacteria limits the diversity of viral species, leading to the expectation that a single phage would outcompete all others. These results demonstrate that it is possible for a single bacterial strain to host a diverse community of phage species and for those species to coexist.
“Knowing how more than one kind of phage can survive over time on a single bacterium could help in designing next-generation phage cocktails,” Pyenson said. “For example, each phage species might attack the bacterium in a different part of its lifecycle and [enable] the whole population to be killed before resistance to the treatment evolves.”
Currently, there are no standard phage therapies for treating bacterial infections either because they failed to kill all their bacterial targets or because the bacteria develop resistance over time. However, some labs are working to change that and insights from this study could be helpful.
In fact, Paul Turner, PhD, a co-author on the study and a professor of ecology and evolutionary biology, is leading a clinical trial at Yale University that uses phages to target Pseudomonas aeruginosa, which can contribute to severe inflammation in the lungs of cystic fibrosis patients. Meanwhile, in the lab of Jonas Schluter, PhD, another study co-author and a professor in the microbiology department at NYU Langone Health, scientists are studying the role of phages in the gut ecosystem of humans and mice. One of their goals is to anticipate the impact of phage administration and design universal phage therapies that work for infections caused by bacteria like Salmonella.
“This work represents a shift in our understanding of phage ecology,” Schluter noted, adding that, “we can now begin to understand the evolution of phages when they are in community with diverse viral species and how this shapes their role in health and disease.”
