Study details a common bacterial defense against viral infection

One of the many secrets to bacteria’s success is their ability to defend themselves from viruses, called . 

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.” 

The large size and elongated configuration of the complex made it difficult to get the full picture of GajB’s functional contributions when bound to GajA, Shen said, leaving the team to make some assumptions about protein roles that have yet to be confirmed. 

“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. 

There is more to learn about bacterial anti-phage defense systems, but this team has already shown that blocking virus replication isn’t the only weapon in the bacterial arsenal. In a previous study, Fu, Shen, Yang and colleagues described a different defense strategy: bacteria programming their own death rather than letting phages take over a community. 

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

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

Related