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The newly discovered bacterial defense system acts as a self-destruct button.

Structural analysis of PCaspase. (A) Top: AlphaFold2 model of full-length PCaspase. Below: A zoom-in of the catalytic diode. (B) Top: AlphaFold2 model of processed PCaspase. Below: Zoom-in of the catalytic dyad, now in a catalytically competent conformation. (C) Folding of the AlphaFold2 multimer of the CHAT domain of SAVED-CHAT with the PCaspase autoinhibitory loop. (D) AF2 model of PCaspase fragment bound to the ChAT domain of SAVED-CHAT. (E) AF2 model of full-length PCaspase and the SAVED-CHAT ChAT domain. (F) Interactions between PCaspase R153 and the ChAT domain from the AF2 model in panels C and D. Credit: science (2024). DOI: 10.1126/science.adk0378

Wageningen researchers have discovered a molecular self-destruct mechanism in a bacterium that lives on seaweed. With this mechanism, bacteria sacrifice themselves upon infection, thereby protecting their brothers and sisters from infection. By reprogramming this mechanism, researchers aim to use it in diagnostic (self) tests. the study Published in science.

The self-destruct mechanism belongs to a bacterial immune system called CRISPR-Cas, which researchers have been studying extensively for a decade. This It is present in about half of all bacteria and exists in various forms.

The newly discovered system triggers self-destruction when it detects an invading virus. Typically, such a virus would use a bacterium as a production factory to replicate. By sacrificing itself, the bacterium prevents spread. “We always suspected that bacteria could use this system to self-sacrificial, but now we have evidence,” says Raymond Stahls, associate professor of microbiology.

to cut to pieces

When a virus injects it. In a bacterium, the immune system sounds the alarm. “This particular immune system of the sea bacterium distinguishes the DNA or RNA of the virus from its own genetic material,” explains Stahls.

When Stahls first studied the mechanism 13 years ago, he discovered that the CRISPR-Cas system cuts RNA. This seemed illogical because viruses constantly produce new RNA. “What an inefficient system, I thought at the time,” Stalls says. “That never sat well with me.”

It now turns out that RNA scissors are just one small step in the larger immune system. ultimately, Activates enzymes that uncontrollably destroy essential biological molecules—RNA, DNA, and proteins—killing the bacterium from the inside out.

Checkpoints

“What makes this whole system so attractive is the inclusion of checkpoints,” Stalls says. “This prevents the bacterium from ‘accidentally’ pressing the self-destruct button.” The trick lies in a molecular domino effect. which regulates the process. When the bacterium detects the invader, the dominoes begin to fall. It then produces signaling molecules that activate other proteins. These proteins, in turn, turn on the “major destroyers.”

During this process, the cell also continuously breaks down the molecules it produces, thus disrupting the domino effect. Self-destruction only proceeds if the bacterium continuously recognizes foreign RNA or DNA. It stops By self-destructing due to false alarms. “It’s a weird chain reaction, like (apoptosis) in humans, but easier,” Stahls says.

The precision of this newly discovered CRISPR-Cas system makes it ideal for development. for diseases. Together with TNO and Staals’ spin-off company, Scope Biosciences, Wageningen researchers will work on developing diagnostic tests in the coming years.

Their goal is to create tests that can simultaneously detect multiple targets, such as diseases, and that are easy to interpret. The PhD candidate will work on the project starting in March. Stalls expects the first diagnostic test to be in hand by 2025.

More information:
Jurre A. Steens et al, Type III-B CRISPR-Cas cascade of proteolytic cleavages, science (2024). DOI: 10.1126/science.adk0378

Reference: Newly discovered bacterial defense system acts as self-destruct button (2024, February 16) Accessed 17 February 2024 at https://phys.org/news/2024-02-newly-bacterial-defense-functions Retrieved from -destruct.html

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