by Researchers from The Rockefeller University have discovered that bacteria have a defensive response called CBASS (cyclic oligonucleotide-based antiphage signaling system) that helps them sense and counter phages, predatory viruses that infiltrate bacterial cells. The findings, published in the journal Nature, shed light on how bacteria detect and defend against phage infections, and may have implications for combating antibiotic resistance in the future.
Although bacteria lack nuclei like animals, they have evolved similar immune responses through the use of specialized enzymes known as cyclases. In animals, the viral-sensing enzyme is called cGAS (cyclic GMP-AMP synthase), while in bacteria, cGAS-like cyclases are key components of the CBASS immune response. The researchers discovered that CBASS cyclases are ancient ancestors of cGAS.
However, the researchers also identified a challenge that bacteria face in detecting phages. Unlike animals, bacteria lack nuclei and therefore cannot rely on the detection of mislocalized DNA as a signal of infection. If CBASS reacted to the mere presence of DNA, it would lead to the bacterium attacking itself. To investigate this conundrum, the researchers focused on the CBASS system in Staphylococcus schleiferi, a bacterium commonly found in the mouths of animals.
Using a set of Staph phages, the researchers found that only RNA produced by the phages during infection was able to trigger an immune response. This specific RNA structure, termed cabRNA (cabernet), binds to the surface of the cyclase and activates the production of a messenger molecule called cGAMP, which in turn activates the CBASS immune response.
The study draws parallels between the CBASS system in bacteria and the cGAS-STING pathway in humans. Both responses involve the detection of viral nucleic acids and the production of messenger molecules that trigger immune responses.
The researchers plan to further study cabRNA to understand its characteristics and its role in phage infections. They are particularly interested in determining how and why phages generate cabRNA and how it interacts with the CBASS enzyme. These findings may provide insights into predicting which phages possess cabRNA and could potentially be used to combat antimicrobial-resistant bacteria in the future.
Dr. Luciano Marraffini, a pioneer in the study of bacterial defense systems, emphasizes the importance of understanding the mechanisms by which bacteria detect and defend against phages. He believes that if we can predict which phages possess cabRNA, we can potentially use them to attack bacteria that have developed resistance to antibiotics. By leveraging the bacteria’s own defense mechanisms, researchers may be able to develop novel strategies to combat antibiotic resistance and enhance the effectiveness of existing treatments.
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