Outer membrane as a drug target for the treatment of GNB infections.

Abstract

Antimicrobial resistance among Gram-negative bacteria poses a critical challenge to global public health. A key factor contributing to this resistance is their unique outer membrane (OM), which serves as a formidable barrier to many antibiotics, particularly hydrophobic and high-molecular-weight compounds. The OM not only limits drug permeability but also houses efflux pumps that actively expel antibiotics, reducing intracellular drug concentrations. This review provides a comprehensive overview of potential OM targets, including Bam, lipopolysaccharide transport, localisation of lipoproteins and Lpx pathways, their roles and antibiotics approved to target these components. In addition, the review presents other non-antibiotic therapies targeting the bacterial OM, including antimicrobial peptides, peptidomimetics, bacteriophages, vaccines and antibody-based therapies.