Targeted bacterial protein degradation using BacPROTAC

Proteolysis-targeting chimeras in bacteria (BacPROTACs) revolutionize antimicrobial strategies by enabling targeted bacterial protein degradation. 

BacPROTACs directly bind their targets and form a ternary complex that enables physical removal instead of inhibition of drug targets; this catalytic mode of action presents a mechanistic advantage.

Not limited to specific binding sites at their target, they can target previously ‘undruggable’ proteins and nonenzymatic substrates, and, compared with classical antibiotics, BacPROTACs are active in low doses, reducing side effects.

They can reduce the pressure to evolve resistance by targeting sites less prone to mutation; mutations in the binding site of the protein of interest are less likely to completely prevent proteolysis.

The modular design of BacPROTACs facilitates high pathogen selectivity and allows broad applications as tools in antibiotic drug discovery or for studying bacterial protein function.

https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(25)00304-4

https://sciencemission.com/BacPROTAC-induced-protein-degradation