Study details common bacterial defenses against viral infections

Advances in technology have enabled the recent identification of proteins involved in these systems, but scientists are looking deeper into what these proteins do.

In a new study, a team at Ohio State University reported on a molecular assembly of a family of proteins called Gaviya, one of the most common antiphage systems, estimated to be used by at least 8.5% of people. , representing up to 18% of all bacterial species on Earth.

The researchers found that one protein appears to have the power to repel phages, but when it binds to a partner protein, the resulting complex cuts the invading phage's genome, rendering it unable to replicate. I found it to be very good.

“We believe that the two proteins need to form a complex to play a role in phage prevention, but we also believe that one protein alone has some antiphage function,” says the study. said co-lead author and postdoctoral researcher Zhangfei Shen. in biochemistry and pharmacology from The Ohio State Medical University. “The complete role of the second protein needs to be further studied.”

The researchers say the discovery further advances scientific understanding of microbial evolutionary strategies and could one day be translated into biomedical applications.

Shen and co-lead author, doctoral student Xiaoyuan Yang, work in the lab of lead author Tianming Hu, assistant professor of biochemistry and pharmacology at The Ohio State University.

The study was published on April 16th. Structural biology and molecular biology of nature.

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

The researchers used cryo-electron microscopy to determine the biochemical structures of GajA and GajB individually, and also the biochemical structures produced when the two combine to form clusters of four molecules of each protein. We determined the biochemical structure of the so-called supramolecular complex GajAB.

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

Although GajA alone showed signs of activity that could disable phage DNA, the complex formed with GajB was much more effective at preventing phages from taking over bacterial cells. did.

“That's the puzzle part,” Yang said. “GajA alone is sufficient to cleave the phage nucleus, but when we incubate it with GajB, it also forms a complex with GajB. Our hypothesis is that GajA recognizes the phage's genomic sequence; GajB enhances that recognition and helps cleave phage DNA.”

The large size and elongated structure of the complex makes it difficult to get a complete picture of GajB's functional contribution when bound to GajA, and the team has several speculations about the protein's role that are yet to be confirmed. said Shen.

“All we know is that GajB helps enhance the activity of GajA, but we still don't know how it works because only about 50% of GajB has been identified on the complex.” said Shen.

One of their hypotheses is that GajB may influence the concentration level of the nucleotide ATP (adenosine triphosphate), an energy source, in the cellular environment. Specifically, by lowering ATP when the presence of phages is detected. That would have the dual effect of amplifying GajA's phage DNA-disabling activity and stealing the energy the phages need to start replicating, Yang said.

Although there is still much to learn about bacteria's antiphage defense systems, this team has already shown that blocking viral replication is not the only weapon in bacteria's arsenal. In a previous study, Fu, Shen, Yang and colleagues described an alternative defense strategy in which bacteria program their own death rather than letting phages take over the community.

This research was supported by the National Institute of General Medical Sciences.

Other co-authors are Jiale Xie, Jacelyn Greenwald, Ila Marathe, Qingpeng Lin, and Vicki Wysocki of The Ohio State University, and Wenjun Xie of the University of Florida.