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Modification of the P. gingivalis lipid A structure. Penta-acylated bisphosphorylated lipid A (left), a moderate TLR4 agonist, is the initial lipid A structure synthesized by P. gingivalis. It is modified to tetra-acylated nonphosphorylated lipid A (right), which is silent for TLR4 activation, by the action of C-1- and C-4′-phosphatases and a 3′-O-deacylase. Inhibition of C-1-phosphatase activity leads to the formation of C-1-phosphorylated tetra-acylated lipid A, a TLR4 antagonist.
