
“Uncovering the mechanism of Zorya’s antiphage defense system and demonstrating its ability to detect and fight phages at early stages of infection represents a major advance in our understanding of this new defense mechanism,” says the new study. say the researchers behind it. Credit: William Brons Petersen.
Imagine a city under constant threat from invaders. The city’s defense system deploys advanced anti-missile defense mechanisms to neutralize threats before they can cause harm. In the microscopic world, bacteria face a similar scenario. For every type of bacteria, both good and bad, there are about 10 types of viruses, also known as “bacteriophages” or simply “phages.” Each of these viruses is tailored to invade bacteria, causing infections in benign bacteria and potentially contributing to antibiotic resistance in malignant bacteria.
Now, a recent study published in Nature by the University of Copenhagen reveals how bacteria use a defense mechanism called Zorya to protect themselves from viral attacks. The system detects and breaks down the virus’s DNA before it can replicate, similar to how a city’s defense system intercepts incoming missiles.
“Many anti-phage defense systems cause cell death, which means the cell self-annihilates and sacrifices itself to prevent the virus from spreading to sister cells.”Remarkably, Zorya “We found that this treats the infection while leaving the cells intact. Obviously this is very powerful for the cells as it ensures their survival,” said Novo, corresponding author of the study. Nicholas Taylor, Associate Professor and Group Leader at the Nordisk Foundation Protein Research Center, explains.
The study was carried out with significant collaboration from researchers at Humboldt University Berlin in Germany, the University of Otago in New Zealand, ETH Zurich in Switzerland, and the University of Oxford in the UK.
promises new treatments
The research shows how bacteria adapt their molecular machinery to evade threats, with potential implications for medicine and biotechnology.
“Uncovering the mechanisms of Zorya’s antiphage defense system and demonstrating its ability to detect and fight phages at early stages of infection represents a major advance in our understanding of this new defense mechanism,” Taylor says. .
The discovery not only improves our understanding of bacterial defense, but also holds promise for the development of new treatments for antibiotic-resistant infections and engineered antiviral systems, Taylor said.
This discovery may also lead to future applications, for example in the design of drugs/inhibitors that can block the defense systems of malignant bacteria and improve clinical phage therapy. It is of particular interest in the fight against antibiotic resistance.
“Furthermore, our findings may stimulate the development of artificial antiviral defense systems that can detect viral infections,” said first author Haidai Hu.
Numerous advanced technologies
To understand how the Zorya defense system works, researchers used cryo-electron microscopy, which helps observe very small structures, and suddenly means changing genes to study function. We used several advanced techniques, including mutagenesis and fluorescence microscopy, which uses glowing markers to see inside. cell. They also utilized proteomics and other functional studies, which study proteins on a large scale.
“We took the genes that make up the Zorya system, ZorAB, ZorC, and ZorD, and inserted them into bacteria that don’t have this defense system. When these modified bacteria are exposed to various viruses, they become infected. “This means the Zorya system can fight the virus directly without killing the bacterial cells,” says Taylor.
“Using cryo-electron microscopy, we investigated the structure of the ZorAB complex in detail. We found that the ZorAB complex acts like a small motor driven by protons. They help detect viral attacks and send signals that activate other parts of the bacterium.”These parts break down the virus’s DNA and stop it from spreading. ”
This research represents a major advance in understanding bacterial defense mechanisms. Future research will focus on further elucidating the molecular details of the Zoriya system and exploring its potential applications in medicine and biotechnology.
Further information: Haidai Hu et al, Structure and mechanism of Zorya antiphage defense system, Nature (2024). DOI: 10.1038/s41586-024-08493-8
Provided by University of Copenhagen
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