Bacterial immunity: inhibiting phages (Introduction)

by David Turell , Saturday, April 27, 2024, 20:35 (12 days ago) @ David Turell

A new study of the molecules at work:

https://phys.org/news/2024-04-common-bacterial-defense-viral-infection.html

"In a new study, a team from The Ohio State University has reported on the molecular assembly of one of the most common anti-phage systems—from the family of proteins called Gabija—that is estimated to be used by at least 8.5%, and up to 18%, of all bacteria species on Earth.

"Researchers found that one protein appears to have the power to fend off a phage, but when it binds to a partner protein, the resulting complex is highly adept at snipping the genome of an invading phage to render it unable to replicate.

"'We think the two proteins need to form the complex to play a role in phage prevention, but we also believe one protein alone does have some anti-phage function," said Zhangfei Shen, co-lead author of the study and a postdoctoral scholar in biological chemistry and pharmacology at Ohio State's College of Medicine. "The full role of the second protein needs to be further studied."

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"The two proteins that make up this defense system are called Gabija A and Gabija B, or GajA and GajB for short.

"Researchers used cryo-electron microscopy to determine the biochemical structures of GajA and GajB individually and of what is called a supramolecular complex, GajAB, created when the two bind to form a cluster consisting of four molecules from each protein.

"In experiments using Bacillus cereus bacteria as a model, researchers observed the activity of the complex in the presence of phages to gain insight into how the defense system works.

"Though GajA alone showed signs of activity that could disable a phage's DNA, the complex it formed with GajB was much more effective at ensuring phages would not be able take over the bacterial cell.

"'That's the mysterious part," Yang said. "GajA alone is sufficient to cleave the phage nucleus, but it also does form the complex with GajB when we incubate them together. Our hypothesis is that GajA recognizes the phage's genomic sequence, but GajB enhances that recognition and helps to cut the phage DNA."

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"'We only know GajB helps enhance GajA activity, but we don't yet know how it works because we only see about 50% of it on the complex," Shen said.

"One of their hypotheses is that GajB may influence the concentration level of an energy source, the nucleotide ATP (adenosine triphosphate), in the cellular environment—specifically, by driving ATP down upon detection of the phage's presence. That would have the dual effect of expanding GajA's phage DNA-disabling activity and stealing energy that a phage would need to start replicating, Yang said."

Comment: this follows closely on Shapiro's work. Not that bacteria modify DNA in this case, but they have other mechanism to protect themselves as free living single cells. Remember the CRISPR mechanism to edit DNA is part of the bacterial defense system and we stole it for our use.