A recent study has provided insights into how a single type of bacteria, which acts as a host for phages, can support a variety of competing phage species. Understanding how multiple viral types can thrive on one bacterium could pave the way for creating advanced viral treatments (phage cocktails) to combat bacterial infections.
Phages, the viruses that infect and kill bacteria, are promising alternatives for treating serious infections, especially those caused by antibiotic-resistant strains. However, there is still limited understanding of how these phages remain in the bacterial populations they target, which complicates the advancement of phage therapies.
A study published on December 13 in the journal Science reveals evidence that a single bacterial species can sustain a diverse range of competing phage species. This research, led by scientists from NYU Grossman School of Medicine, Oxford, and Yale University, demonstrated that various phage species can stably coexist on a genetically uniform strain of E. coli, a bacterium normally found in the human gut, some of which can cause illness.
The study found that even in competition, different phage species were drawn to either the slower or faster growing bacterial cells that appeared randomly. As a result, each phage species could occupy a distinct niche within the same host, allowing for stable coexistence. For instance, some cells may slow their growth due to a scarcity of nutrients. In this research, two phage species, referred to as N and S, thrived together because N excelled in fast-growing bacterial cells, while phage S was more suited to slower-growing ones.
Phage therapy developers aim to address the challenge seen in antibiotic treatments, where an antibiotic may eliminate most bacteria, but some resistant strains survive. These remaining bacteria are particularly concerning because they can resist available treatments.
“Understanding how multiple phage types can persist on a single bacterium could aid in designing next-generation phage cocktails,” stated Nora Pyenson, PhD, the first author of the study and a postdoctoral researcher in Jonas Schluter’s lab at NYU Langone Health. “For instance, different phage species might target various stages of the bacterium’s lifecycle, potentially eliminating the entire population before resistance can develop.”
Dr. Pyenson added, “Currently, no phage therapies have become the standard for treating bacterial infections, largely because previous attempts with single phages failed to eradicate all targeted bacteria or because the bacteria eventually evolved to resist the treatment, similar to the way they resist antibiotics.”
Research laboratories are exploring phage treatments as a viable alternative to antibiotics. For example, Dr. Paul Turner of Yale University is leading a clinical trial using phages to combat Pseudomonas aeruginosa, which can lead to severe lung inflammation in cystic fibrosis patients. Meanwhile, Dr. Schluter’s lab is investigating the role of phages in the human and mouse gut ecosystems to inform future therapies for infections like Salmonella. An overarching goal is to predict the effects of administering phages and create therapies that function universally across many patients, unlike current treatments that must be tailored to individuals.
Importance of Phage Ecology
Understanding diversity among species is a vital question in ecology and evolutionary science. A significant contributor to diversity, from birds to plants to bacteria, is how species can coexist while competing for resources. Historically, however, viruses were not considered in this “social” framework.
The research team tested the long-standing view that genetic diversity among bacteria restricts the variety of viral species. This assumption led to the expectation that a single phage type would eliminate all competitors. Yet, just as multicellular organisms can host numerous bacterial species in their microbiome, this study demonstrates that a singular bacterial strain can also harbor a diverse community of phage species.
“Our findings contribute to the increasing field of studying the social interactions of viruses,” noted Dr. Pyenson. “We often perceive viruses solely in terms of their effects on the host, overlooking their interactions with other viral species. These phage communities exemplify how diversity can arise even among the simplest biological entities.”
Interestingly, a diverse bacterial population in the human gut is a hallmark of health, as this rich microbiome is better equipped to fend off invading diseases. Similarly, the variety of viruses that inhabit gut bacteria is emerging as a crucial factor in health, with abnormal phage mixes believed to play a role in conditions like sepsis.
“This research signifies a shift in our comprehension of phage ecology,” said Dr. Schluter, a professor in the Department of Microbiology at NYU Langone. “Thanks to Nora’s efforts, which she managed through a pandemic and across four laboratories, we can now begin to understand how phages evolve in environments rich in diverse viral species, shaping their roles in health and disease.”
Alongside Drs. Pyenson and Schluter at NYU Langone, and Dr. Turner at Yale, study contributors included Asher Leeks and Odera Nweke from Yale’s Department of Ecology and Evolutionary Biology; Joshua Goldford from the California Institute of Technology’s Division of Geological and Planetary Sciences; Kevin Foster from the University of Oxford’s Department of Biology; and Alvaro Sanchez from the Institute of Functional Biology & Genomics, CSIC & University of Salamanca in Spain. Drs. Foster and Sanchez served as corresponding authors with Dr. Pyenson.
Funding for portions of this research was provided by the Life Science Research Foundation and the Simons Foundation for Dr. Pyenson, and through a New Innovator Award to Dr. Schluter from the National Institute of Autoimmune and Infectious Diseases (NIH award DP2AI164318).
