Abstract
The rapid emergence of antibiotic-resistant superbugs poses a significant global health threat. Gram-negative bacteria are the primary culprits due to their robust, tripartite cell envelope. This review explores the emerging role of the trans-envelope Tol-Pal system in maintaining envelope integrity, by connecting envelope layers and serving as a protein interaction hub. Targeting the Tol-Pal system offers a promising approach for the development of novel envelope-disrupting antimicrobials.