This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A new tool to mutate bacteriophages—viruses that infect bacteria—provides a "big leap" forward in our understanding of how they function and our ability to harness their full potential. Developed by researchers in the Department of Microbiology and Immunology at the University of Otago – Ōtākou Whakaihu Waka in New Zealand, the method is featured in Nature Microbiology.
Senior author Professor Peter Fineran says bacteriophages, or simply phages, have "huge potential" to combat the antimicrobial resistance crisis and promote sustainable agriculture as an alternative to agrochemicals because they can destroy bacteria. "But our knowledge of phages is probably like the understanding of antibiotics back in the 1950s. Many phage genes are currently in the area of microbial dark matter—encoding functions we just don't understand—which is limiting our ability to use phages in health care and biotechnology.
"This new development is a big leap in how we can rapidly understand phage biology and then use that knowledge to make phages work better to help achieve our goals." Co-lead author Dr. Manuela Fuchs says the new method allows for genome-wide mutagenesis of bacteriophages using CRISPR-Cas technology. The researchers used transposon insertion sequencing—a technique that uses a mobile piece of DNA that can jump into and disrupt a gene—combined with CRISPR-anti-CRISPR-based selection to select phages that have been mutated.
This allows them to identify genes that are essential and genes that are nonessential for phage survival. "Once we had that established, we thought we could expand the technique and also use it to add genes directly into the phage genomes. We essentially found it is possible to load additional genes on that transposon, not just our anti-CRISPR protein.
While we added a fluorescent marker, it could be used to, for example, add additional anti-defense genes to phages to improve their therapeutic potential," Fuchs says. Leah Smith says the method enables genes to be inserted automatically while maintaining phage function. "This is a systematic, broadly applicable and cost-effective way to not only investigate gene function, but also rapidly engineer phage genomes.
"This opens up new opportunities for both fundamental research and future therapeutic development." One example involves biofilms, which can cause hard-to-treat infections on prosthetic implants and medical devices. "With this new technique, we could quickly equip phages with more tools to counter some bacterial defenses so that they can be harnessed to kill pathogens more easily," Smith says. Defining the essential genome of diverse phages with phage Tn-seq, Nature Microbiology (2026).
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