Immunity system complexity: how bacteria fight phages (Introduction)

by David Turell , Wednesday, November 15, 2023, 19:30 (163 days ago) @ David Turell

Sensing a specific RNA viral structure is involved:

https://phys.org/news/2023-11-bacteria-viral-invasion-immune-defenses.html

"There's no organism on Earth that lives free of threat—including bacteria. Predatory viruses known as phages are among their most dire foes, infiltrating their cells to replicate and take over. Bacteria have evolved an array of strategies to counter these infections, but how they first spot an invader in their midst has long been a mystery.

"Now researchers in the Laboratory of Bacteriology at The Rockefeller University have discovered that bacteria sense phages via a defensive response called CBASS that detects viral RNA—findings that one day may help counter the threat of antibiotic resistance.

"'How CBASS is activated by phage infection has been a big unknown in our field for many years," says Luciano Marraffini, head of the lab. "Until now, no one has understood what triggers the bacteria to initiate the CBASS immune response."

"Some core immune functions are shared across distantly related domains of life, from eukaryotes (organisms with a membrane-bound nucleus) like mammals, plants, and fungi to prokaryotes (those without such membranes) like bacteria and archaea. These immune responses must've evolved early in the existence of life.

"One conserved characteristic is a viral sensing mechanism that relies on a specialized enzyme known as a cyclase. In animals, it's called cGAS (cyclic GMP-AMP synthase). In bacteria, cGAS-like cyclases are central components of the CBASS (cyclic oligonucleotide-based antiphage signaling system) immune response. Both were only discovered in the past decade.

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"However, because bacteria lack nuclei, they must take another approach. If CBASS reacted to the mere presence of DNA, it would result in rampant autoimmunity, or the bacterium attacking itself, Banh says.

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"The experiment revealed that only RNA produced during phage infection was able to trigger an immune response. "It was very clearly viral RNA that was generated during infection," says Roberts. "So instead of sensing a DNA mislocalization, like cGAS does, CBASS senses a specific RNA structure. This specificity is amazing." (my bold)

"They coined the newly identified, hairpin-shaped molecule cabRNA (pronounced "cab-R-N-A" or alternatively, "cabernet"), for CBASS-activating bacteriophage RNA. The molecule binds to a surface of the cyclase, triggering the production of a messenger molecule called cGAMP that activates the CBASS immune response.

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"Here, too, there are parallels to how the analogous system operates in humans. After detecting viral DNA, cGAS also triggers the production of cGAMP, which induces the immune system to produce Type I interferons. That antiviral signaling pathway is known as cGAS-STING."

Comment: a clear representation of how evolution passes down useful mechanisms. Note my bold. The narrow degree of specificity is truly amazing. Another example of an IC mechanism.