Researchers have developed a new method, Phage Tn-seq, that can quickly pinpoint which genes bacteriophages need to function and allow scientists to add new genetic material, potentially enabling researchers to engineer phages better able to attack harmful bacteria.
Bacteriophages, or phages, are viruses that infect and kill bacteria, offering a potential alternative to antibiotics at a time when drug-resistant infections threaten global health. But despite decades of study, the functions of many phage genes remain unknown, limiting their medical use.
Now, researchers from the University of Otago and other institutions have developed a method to investigate phages in greater detail. The approach, called Phage Tn-seq, combines transposons, mobile DNA segments, with CRISPR-Cas selection and DNA sequencing. Transposons insert randomly into the phage genome, disrupting gene function. By sequencing the DNA, scientists can identify which genes are essential for the virus to replicate.
The technique also enables the insertion of new genetic material. As a demonstration, the team added a gene for green fluorescent protein, causing infected bacteria to glow green. The researchers suggest similar methods could be used to introduce genes that make phages more effective at killing bacteria, including those protected by biofilms, sugar-based layers that make infections difficult to treat with antibiotics.
Phage therapy has been used for a century, but its use declined after the development of antibiotics. Antibiotic resistance is prompting renewed interest in phage-based treatments. In New Zealand, phage therapy is not routinely available partly because of regulatory hurdles and gaps in understanding these viruses.
The researchers say the new technique will not immediately overcome these barriers, but could lay the groundwork for a wider range of phage applications.
Analysis
Why This Matters
- Antibiotic resistance is a fast-growing global threat; the new method could speed up development of phage-based alternatives.
- The technique could enable scientists to engineer phages that break down bacterial biofilms, tackling a major cause of hard-to-treat infections.
- Faster identification of essential phage genes may help researchers adapt phages for personalised therapy, matching specific viruses to a patient's infection.
Background
Phages are naturally occurring viruses that infect and destroy bacteria. They were used to treat bacterial infections before the widespread adoption of antibiotics in the mid-20th century. The rise of antibiotic resistance, exacerbated by overuse of these drugs, has led to renewed interest in phage therapy. However, regulatory systems and limited scientific understanding have constrained its use.
Key Perspectives
(This section omitted because the source reports only the researchers' position, with no alternative perspective.)
What to Watch
- Whether the method can be applied to a wide range of phages and bacterial hosts, as the researchers intend.
- The potential for engineered phages to be tested in clinical settings, with a focus on biofilm-associated infections.
- Policy changes in countries like New Zealand that could permit routine phage therapy.
Checked
9 claims in this story checked against 1 source: 7 supported.
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- SupportedThe new method could help improve the fight against antibiotic resistance by enabling phages to attack harmful bacteria.The Conversation – Articles (AU): “This might eventually help researchers engineer phages that are better at attacking harmful bacteria – opening up possibilities for treating infections that conventional antibiotics struggle against.”
- SupportedPhage Tn-seq can quickly identify genes phages need and insert new genetic material.The Conversation – Articles (AU): “We’ve developed a method to pinpoint which genes phages need to function, and to insert new genetic material into their genomes within days.”
- Not in the sourcesThe researchers who developed the method are from the University of Otago and other institutions.The Conversation – Articles (AU): “Now, our new research offers a way to investigate them in greater detail.”
- SupportedPhage Tn-seq combines transposon insertions with CRISPR-Cas selection and DNA sequencing to identify gene functions.The Conversation – Articles (AU): “By applying CRISPR-Cas selection, we could eliminate phages that hadn’t received the transposon. This left us with a pool of phages carrying different mutations, which we could study to identify the function of their genes.”
- SupportedThe team added a gene for green fluorescent protein, making infected bacteria glow green.The Conversation – Articles (AU): “We then added a gene encoding green fluorescent protein, causing infected bacterial cells to glow bright green under a microscope.”
- Partly supportedPhage therapy’s medical use declined after antibiotics were developed.The Conversation – Articles (AU): “But with the arrival of antibiotics, inconsistent results from early phage treatments and the onset of the Cold War, their medical use declined in Western countries.”
- SupportedResearchers could use the technique to make phages more effective against bacteria in biofilms.The Conversation – Articles (AU): “Using Phage Tn-seq, researchers might engineer phages to produce proteins that break down these layers while attacking the bacteria themselves.”
- SupportedPhage therapy is not routinely available in New Zealand partly because of regulatory hurdles and gaps in understanding phages.The Conversation – Articles (AU): “In New Zealand, however, phage therapy is not routinely available as a treatment option, partly because of regulatory hurdles and gaps in our understanding of these viruses.”
- SupportedThe researchers say their technique will not immediately overcome those barriers but could lay groundwork for wider applications.The Conversation – Articles (AU): “Our research won’t overcome those barriers overnight. But by giving scientists new tools to understand and modify phages, it could lay the groundwork for a wider range of applications.”
