Targeting Antiphage Systems in E. coli: Inhibitor Design Using BindCraft

Phage viruses that prey on bacteria are being disarmed by the bacteria's own immune-like defense systems, and this project aims to design small-molecule inhibitors that switch those defenses off. The problem is straightforward: antibiotic-resistant bacteria are a growing threat, and one promising alternative—phage therapy, which uses viruses to kill bacteria—often fails because bacteria have evolved sophisticated antiphage defense systems that block the infection. Researchers have identified thousands of these defense systems in *E. coli* genomes, but no one has systematically designed drugs to disable them. This project uses a computational tool called BindCraft to model how key bacterial defense proteins interact with each other, then predicts which small molecules could jam those interactions. If successful, the work would make phage therapy far more reliable against drug-resistant *E. coli* infections, which cause everything from urinary tract infections to sepsis. The same approach could eventually be extended to other bacterial pathogens, offering a new way to keep phage therapy effective where antibiotics have failed.