PROTAC antibiotics: the time is now.

BacPROTACs demonstrate that linking a target directly to a bacterial protease complex can promote target degradation. BacPROTACs successfully bypass the 'middleman' E3 ligase, providing an entry strategy for the generation of antibacterial PROTACs. We speculate that antibacterial PROTACs will not only expand the target space but may also improve treatment by allowing dosage reduction, stronger bactericidal activity and activity against drug-tolerant 'persisters.'