LPS O-antigen polysaccharide length impacts outer membrane permeability of enteric gram-negative bacteria

The outer membrane (OM) of bacteria like <i>Escherichia coli</i> and <i>Shigella flexneri</i> forms a barrier that protects cells against antibiotics and immune effectors. The surface-exposed leaflet is filled by lipopolysaccharides (LPS) decorated with long "O-antigen" (O-Ag) polysaccharides. The benefit of covering the surface with O-Ag is well appreciated; these long polysaccharides shield against host assaults. Our study reveals a hidden cost to these long O-Ag polysaccharides: transporting and assembling LPS modified with O-Ag compromises integrity of the OM antibiotic barrier, rendering bacteria vulnerable to antibiotics. Cells must balance O-Ag across two parameters-protection from the host and preserving OM integrity. Our findings also present an inherent benefit to not producing O-Ag, a common feature among diverse bacterial pathogens.