Are outer-membrane targets the solution for MDR Gram-negative bacteria?

The outer membrane (OM) of Gram-negative bacteria confers a significant barrier to many antibac-terial agents targeting periplasmic and cytosolic functions. 'Synergist' approaches to disrupt the OM have been hampered by poor specificity and accompanying toxicities. The OM contains proteins required for optimal growth and pathogenesis, including lipopolysaccharide (LPS) and capsular polysaccharide (CPS) transport, porins for uptake of macromolecules, and transporters for essential elements (such as iron). Does the external proximity of these proteins offer an enhanced potential to identify effective therapies? Here, we review recent experiences in exploiting Gram-negative OM proteins (OMPs) to address the calamity of exploding antimicrobial resistance. Teaser: Multidrug-resistant (MDR) Gram-negative bacteria are a growing crisis. Few new antimicro-bial chemotypes or targets have been identified after decades of screening. Are OMP targets a solution to MDR Gram-negative bacteria?