The emergence and global spread of antimicrobial resistance (AMR) is a significant problem threatening human, plant and animal health. Central to the problem of AMR Gram-negative bacteria, which are resistant to many antibiotics due to their impermeable outer membrane (OM). Antibiotic killing in Gram-negative bacteria is hypothesised to be linked to the disruption of OM protein assembly, comprised of five membrane-associated proteins BamA-E. The essentiality and surface exposed nature of BamA has become an attractive target for the development of novel antibiotics. A promising new avenue for antibiotic development focuses on lectin-like bacteriocins (Llps), bactericidal proteins naturally secreted by Gram-negative bacteria to kill their competitors. In this project, we aim to turn the inherent defence system of Gram-negative bacteria on itself, by developing Llps that target OM protein assembly to rapidly kill cells. Utilising Pseudomonas aeruginosa, a ubiquitous and opportunistic as a model organism, we aim to uncover the molecular mechanism of Llp killing. This will be achieved using a combination of phenotypic and polyomics to (i) identify the morphological consequences of Llp treatment, (ii) determine the molecular consequences of Llp treatment on cellular homeostasis, and (iii) uncover cell envelope stress signalling pathways activated due to the OM protein assembly dysregulation. Whilst this project will provide a holistic insight into the understanding of how and why Llps produced by Pseudomonas sp are so cytotoxic, the universal link between exploiting the cells own natural defence system highlights the broader implications to develop new therapeutic strategies against all gram-negative pathogens.