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Writer's pictureSTEM Today
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Engineering Viruses to Combat Deadly Pathogens

February 2024

Milan Even


Northwestern University researchers have achieved a significant breakthrough by modifying the DNA of bacteriophages, or "phages," a class of viruses that infect bacteria. In this study, the researchers harnessed the power of these engineered phages to trigger self-destruction within the deadly bacterium Pseudomonas aeruginosa. This bacterium is notorious for its high resistance to antibiotics, posing a severe threat to global health. The innovative approach of manipulating phage DNA marks a crucial step toward developing novel therapeutics designed to combat antibiotic-resistant bacterial infections, addressing a pressing need as antimicrobial resistance continues to escalate worldwide.


The dark spots in the dishes mark areas where the viruses burst out of the bacteria, effectively killing them. Credit: Cole Wilson

Phage therapy, an emerging field of research, holds promise as an alternative to traditional antibiotics. The ability to selectively target specific bacterial infections without disrupting the body's natural balance is a key advantage of phage therapy. The study not only offers insights into the little-explored realm of phage biology but also provides a foundation for engineering designer viruses with precise traits. Understanding the inner workings of phages in real-time as they are being engineered represents a cutting-edge aspect of the project, contributing to the broader understanding of these microscopic agents.


The rise of antimicrobial resistance has created an urgent and growing threat to the global population. According to the Centers for Disease Control and Prevention (CDC), nearly 3 million antimicrobial-resistant infections occur annually in the United States alone, resulting in over 35,000 deaths. In this context, exploring alternative strategies to antibiotics has become imperative. While billions of phages exist, scientists have limited knowledge about them, making phages a relatively uncharted territory in microbiology. The motivation to study and understand phages is driven by the urgent need for effective alternatives to traditional antimicrobials.


Schematic representation of the experimental procedure. Using direct extraction of the phage genome or the construction of overlapping fragments amplified by PCR, we were able to clone or construct the phage genome in yeast and maintain it using yeast elements. Next, extraction of yeast DNA and digestion by restriction enzymes allowed us to obtain full-length phage DNA that is free from yeast elements. Finally, PA transformation permitted us to obtain rebooted phage particles.

Phage therapy has the potential to revolutionize infection treatment by offering specificity comparable to antibiotics. Unlike broad-spectrum antibiotics that can disrupt the entire gastrointestinal tract, phage therapy can be designed to affect only the targeted infection. The study focused on Pseudomonas aeruginosa, a highly drug-resistant bacterium, responsible for severe infections, particularly in individuals with compromised immune systems. The success of the engineered phages in penetrating and killing this bacterium highlights the potential of phage therapy in addressing urgent healthcare challenges.


Moving forward, the researchers plan to continue modifying phage DNA to optimize potential therapies. The study lays a foundation for further investigations into tailoring phage therapies for specific bacterial infections, offering hope in the battle against antibiotic-resistant pathogens.





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