Targeting bacterial degradation machinery as an antibacterial strategy

Radoslav Petkov; Amy H Camp; Rivka L Isaacson; James H Torpey

doi:10.1042/BCJ20230191

Targeting bacterial degradation machinery as an antibacterial strategy

Biochem J. 2023 Nov 15;480(21):1719-1731. doi: 10.1042/BCJ20230191.

Authors

Radoslav Petkov¹, Amy H Camp², Rivka L Isaacson¹, James H Torpey¹

Affiliations

¹ Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
² Department of Biological Sciences, Mount Holyoke College, 50 College Street, South Hadley, Massachusetts 01075, U.S.A.

Abstract

The exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of specific proteins of interest through the hijacking of the ClpCP machinery. These strategies represent an important emerging avenue for combatting antimicrobial resistance.

Keywords: AAA proteins; PROTACs; antibiotic resistance; degradation.

Publication types

Review

MeSH terms

Anti-Bacterial Agents* / pharmacology
Bacteria
Biological Products*
Down-Regulation
Peptide Hydrolases

Substances

Anti-Bacterial Agents
Biological Products
Peptide Hydrolases