Despite antibiotics, bacterial infections still represent a major challenge to human health as bacteria have been developing resistance to most of the currently available antibiotics. Ideally, we need to develop not only new antibiotics but also explore novel strategies to fight pathogenic bacteria. Targeted protein degradation (TDP) as a method for fighting antibiotic-resistant bacteria has already been proposed for Mycobacteria. A new study in EMBO reports shows a novel variant of TPD that is applicable to both Gram-negative and Gram-positive bacteria, using the conserved AAA+ protease ClpXP (Izert-Nowakowska et al, 2025). This could potentially expand the toolkit for fighting antibiotic resistance to a broader class of pathogens.