A groundbreaking discovery by a joint research team from the Institute of Biophysics of the Chinese Academy of Sciences and the Beijing Institute of Technology, published on May 8, reveals a pivotal mechanism in bacterial antiviral defense. The team has elucidated how bacteria employ cyclic dinucleotides (CDNs) to combat viral infections, potentially revolutionizing antibacterial research.
The study focuses on the cyclic oligonucleotide-based anti-phage signaling system (CBASS), a crucial innate antiviral defense mechanism in bacteria. Researchers found that CDNs, synthesized during CBASS activation, trigger the assembly of phospholipase effectors. These effectors disrupt membranes, executing the downstream immune response.
By examining CapE, a representative phospholipase effector, the team determined its structure in various states using advanced techniques like cryo-electron microscopy and X-ray crystallography. The findings reveal that CDN binding causes a dramatic structural change in CapE, exposing its catalytic site and promoting polymerization into filaments. These filaments then become active platforms for phospholipid cleavage, rapidly activating the bacterial immune response.
Further experiments confirmed that both filament formation and enzymatic activity are essential for CBASS-mediated membrane disruption and programmed cell death. This discovery establishes a direct molecular link between CDN sensing and effector activation. It offers a unified model for how CDNs trigger membrane-targeting immune responses, highlighting filament formation as a key strategy for regulating enzymatic activity across diverse immune systems.
This research not only deepens our understanding of bacterial immunity but also opens new avenues for developing novel antibacterial strategies. By targeting the CBASS system or the filament formation process, scientists could potentially create new therapies to combat bacterial infections, offering hope in the face of growing antibiotic resistance.