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Researchers in the Raman Lab in the Department of Biochemistry developed a tool to identify short patterns in the genomes of bacteriophages that make phages effective at killing bacteria. Here’s the run down on their latest research, published in Science Advances:
- Researchers are studying bacteriophages — viruses that infect bacteria — to identify short genetic sequences that are key to phages’ infectious abilities.
- A new tool developed in the Raman Lab can pinpoint patterns in sequences previously too short to identify.
- The researchers demonstrated that these patterned sequences can be engineered into phages to enhance their ability to kill infectious bacteria such as E. coli implicated in major food-borne outbreaks.
What background information do you need to know?
Over millions of years, bacteria and bacteriophages — viruses that infect bacteria — have driven their own evolution: bacteria evolve to evade infection, and, in turn, phages develop ways to invade their bacterial host.
Amid this rapid evolution, some short genetic sequences have patterns that are passed down through generations. These sequences, called motifs, that have remained relatively unchanged over the course of evolution may be responsible for making an organism more fit to survive. Scientists are working to identify such motifs in phages to evaluate how they confer an advantage to phage survival. By doing so, they can engineer and deploy phages that are even more effective at attacking bacteria than phages found in nature. Their goal is to treat antibiotic-resistant bacterial infections.
Why does the drug-protein structure matter?
Unfortunately, motifs are too short to be recognized by existing technologies that sift through libraries of phage genomes. Without more sensitive technology, finding motifs — and then identifying which motifs confer meaningful benefits — can be like looking for a needle in a haystack.
How have scientists made progress?
Researchers in the Raman Lab used a tool they developed to find thousands of motifs that are conserved across families of phages. The tool, called Metagenomic Sequence Informed Functional Scoring (Meta-SIFT), uses large datasets of phage genomes to identify motifs. The scientists experimentally tested motif functions in a model phage and identified how some of the motifs result in phages that more effectively kill bacteria.
They then tested the engineered phages against a highly pathogenic strain of Escherichia coli linked to major foodborne outbreaks in in the United States in 2013, 2016, and 2024. These phages successfully eliminated E. coli in a lab setting. The team continues to explore the potential for Meta-SIFT data to be translated into therapeutic applications for E. coli and other infectious bacteria.
Written by Renata Solan.
In Research In Brief: The What, Why, and How, we explore new research from the UW–Madison Department of Biochemistry to learn more about the world around us — and inside us.
This edition of Research in Brief: The What, Why, and How is based on the following publication: Huss, Kieft, Meger, Nishikawa, Anantharaman, and Raman. Engineering bacteriophages through deep mining of metagenomic motifs. Science Advances, Apr. 2025, 11(16):eadt6432.
This research was funded in part by the National Institute of Allergy and Infectious Disease (NIAID), the National Institute of General Medicine Sciences of the National Institutes of Health.