As antibiotic resistance accelerates into a global health emergency, scientists are almost turning to taste, bacteria-killing viruses.
Now, a new study from the University of Southampton reveals that these viruses known as phages are designed to overturn the sophisticated defenses of antibiotic-resistant bacteria.
This breakthrough shines light on previously unknown bacterial defense mechanisms and is an important step towards developing next-generation therapies that could replace broken antibiotics.
Phage: Natural Bacterial Predators
Fungi, often referred to as “bacteria-eating people,” is a virus that targets and destroys bacterial cells while leaving human cells intact.
Their unique ability to penetrate and kill bacteria makes them promising candidates in the ongoing search for treatment for drug-resistant infections.
The phage resembles a microscope syringe on the leg. When they latch into the bacteria, they inject genetic material and hijack the cell’s machinery to replicate themselves.
This will eventually rupture the bacterial cells, releasing new waves of phage, continuing the assault.
However, bacteria have evolved complex defenses to drive away invaders of these viruses. One of the most common systems is a system that scientists call Kiwa.
Kiwa: Molecular Firewall
Named after the protected marine god of Maori mythology, Kiwa acts as a biological security system.
Dr. Franklin Nobrega, an associate professor at the University of Southampton and a Southampton National Institute of Laboratory (NIHR) Southampton Biomedical Research Center (BRC) unit, explained:
Researchers at Southampton used cutting-edge imaging techniques to decipher this complex defense mechanism. They discovered that Kiwa is made up of two molecular components, Kwaa and Kwab.
KWAA functions as a sensor to detect invading phages, whereas KWAB functions as a response unit, binding to and abolishing phage DNA before grasping control of bacterial cells. This two-step mechanism effectively constructs a molecular barrier against phage attack.
Phage fights back with a decoy
However, phages like digital hackers have developed anti-measurements. Some release mimetic proteins that trick KWAB into responding to false threats.
While Kiwa targets the decoy, the actual phage DNA slips in undetected, starting a destructive task within the bacteria.
Despite this clever tactic, Kiwa is not the only line of defensive bacteria. Another mechanism called RecBCD can also identify and destroy phage DNA.
Phage decoys can deceive the kiwa or RECBCD individually, but when both systems work together, they fail and present a double lock that is much more difficult to choose.
The urgent need to tackle antibiotic resistance
Antibiotic resistance is the heightened public health crisis.
Experts predict that drug-resistant infections could cause up to 10 million deaths per year by 2050, and the NHS has already spent around £180 million a year in such cases. With few new antibiotics under development, phage therapy is being reexamined as a viable solution.
The Southampton team is actively collecting and cataloging phages that can bypass bacterial defenses. To date, they have identified over 600 potential candidates.
The New Citizen Science Initiative is inviting the public to send samples of dirty water, a rich source of phage and bacteria, to expand their research.
Nobrega added: “A deeper understanding of how these defense mechanisms work will explain how to exploit weaknesses and select the phage that is most likely to break bacteria.
“The more samples you have, the more likely you are to find the best phage for your job.”
Towards a phage-driven future
Understanding how bacterial defense systems like Kiwa work and how phages neutralize them can be key to developing effective treatments for antibiotic-resistant infections.
By exploiting the evolutionary arms race between phages and antibiotic-resistant bacteria, scientists hope to stay one step ahead in protecting human health.
As research continues, these insights may change how we approach some of the world’s most lethal bacterial threats that provide a new line of defense when antibiotics fail.
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