Targeting deubiquitinating enzymes (DUBs) and ubiquitin pathway modulators to enhance host defense against bacterial infections.

The rise of antibiotic-resistant bacterial pathogens poses a critical global health challenge, necessitating innovative therapeutic approaches. This study explores host-targeted therapies (HTTs) by focusing on deubiquitinating enzymes (DUBs), essential modulators of the ubiquitin-proteasome system (UPS) that regulate host-pathogen interactions during many bacterial infections. Using -infected macrophages as a model, we identified UPS modulators that enhance bacterial clearance and observed significant changes in DUB expression, particularly USP25, USP46, and Otud7b.