Structure of lipid A and the polymorphic regulation outer membrane lipid composition. (A) Lipid A in S. Typhimurium is an acylated and phosphorylated disaccharide of glucosamine linked by a β-1′,6-glycosidic bond. Unmodified lipid A exhibits four primary R-3-hydroxymyristate chains, where the two distal chains are esterified with secondary acyloxyacyl groups. S-2-OH can be incorporated into a myristate chain, and a palmitate chain (C16) can be incorporated as a regulated modification. Modification of the lipid A phosphate groups with phosphoethanolamine (pEtN) and l-4-aminoarabinose (l-Ara4N) can also be observed. (B) Cylindrical and conical lipid A molecular shapes can be assumed by various lipid A subtypes, and these are predicted to adopt either lamellar (L)- or inverted type II hexagonal (HII)-phase structures, respectively. A balanced mixture of these two types of lipid A structures helps to determine the aggregate bilayer architecture of the outer membrane. Cubic phases (not shown) are also possible. Magenta circles represent glucosamine units, small red circles represent phosphate moieties, the blue diamond represents l-Ara4N, the green oval represents pEtN, and black wavy lines represent acyl chains.