Andrea Milelli, Simone Raimondi, Somayeh Asgharpour, Jean‐Denis Docquier, Francesca Spyrakis
The discovery of antibiotics revolutionized modern medicine, enabling the treatment of once-deadly bacterial infections. However, the rise of antibiotic-resistant bacteria has severely limited their effectiveness, making antimicrobial resistance (AMR) a major global health challenge. Developing new antibiotics with novel mechanisms of action is notably difficult. A promising approach is targeted protein degradation (TPD), a technology that has transformed drug discovery and shown success in cancer, neurodegenerative diseases, and immunology. In this review, we explore the potential of TPD to create next-generation antibacterials, its advantages over conventional antibiotics, and current research on prokaryotic protein degradation systems and BacPROTAC molecules.