June 23, 2022

BacPROTACs mediate targeted protein degradation in bacteria

Scientists in the the lab of Tim Clausen at the IMP and their international collaborators present an innovative and broadly applicable strategy pointing to an entirely new type of antibiotics: bacterial proteolysis targeting chimeras, or BacPROTACs. They show how these molecules can be designed to cause the selective degradation of virtually any bacterial protein, potentially leading to the bacterial cell’s death. Their study has now been published in the journal Cell.

BacPROTACS are composed of two linked modules: a target-binding module, which selectively attaches to a protein of interest, and a degradation-inducing module, which tethers the target protein to a bacterial protein shredder that disentangles the target protein before chopping it up into pieces. In this study, the authors demonstrate as a proof of concept that the BacPROTACs’ modular structure is versatile enough to be adjusted to different target proteins and different bacterial species, a promising finding for the future of antibiotic discovery.


See the full story in the IMP news here.



Francesca Ester Morreale, Stefan Kleine, Julia Leodolter, Sabryna Junker, David M. Hoi, Stepan Ovchinnikov, Anastasia Okun, Juliane Kley, Robert Kurzbauer, Lukas Junk, Somraj Guha, David Podlesainski, Uli Kazmaier, Guido Boehmelt, Harald Weinstabl, Klaus Rumpel, Volker M. Schmiedel, Markus Hartl, David Haselbach, Anton Meinhart, Markus Kaiser, Tim Clausen:

BacPROTACs mediate targeted protein degradation in bacteria.

Cell. 2022 June 3.
DOI: 10.1016/j.cell.2022.05.009


Graphical Abstract. https://doi.org/10.1016/j.cell.2022.05.009