If lipid A, part of the LPS, enters the circulatory system it causes a toxic reaction by activating TLR 4. Lipid A is very immunogenic and causes an aggressive response by the immune system. The sufferer will have a high temperature and respiration rate and a low blood pressure. This may lead to endotoxic shock, which may be fatal.
The biogenesis of the outer membrane requires that the individual components are transported from the site of synthesis to their final destination outside the inner membrane by crossing both hydrophilic and hydrophobic compartments. The machinery and the energy source that drive this process are not yet fully understood. The lipid A-core moiety and the O-antigen repeat units are synthesized at the cytoplasmic face of the inner membrane and are separately exported via two independent transport systems, namely, the O-antigen transporter Wzx (RfbX) and the ATP binding cassette (ABC) transporter MsbA that flips the lipid A-core moiety from the inner leaflet to the outer leaflet of the inner membrane. O-antigen repeat units are then polymerised in the periplasm by the Wzy polymerase and ligated to the lipid A-core moiety by the WaaL ligase.
The LPS transport machinery is composed of LptA, LptB, LptC, LptD, LptE. This supported by the fact, that depletion of any of one of these proteins blocks the LPS assembly pathway and results in very similar outer membrane biogenesis defects. Moreover, the location of at least one of these five proteins in every cellular compartment suggests a model for how the LPS assembly pathway is organised and ordered in space.
LptC is required for the translocation of lipopolysaccharide (LPS) from the inner membrane to the outer membrane. LptE forms a complex with LptD, which is involved in the assembly of LPS in the outer leaflet of the outer membrane and is essential for envelope biogenesis.
^Feldman MF, Marolda CL, Monteiro MA, Perry MB, Parodi AJ, Valvano MA (December 1999). "The activity of a putative polyisoprenol-linked sugar translocase (Wzx) involved in Escherichia coli O antigen assembly is independent of the chemical structure of the O repeat". J. Biol. Chem.274 (49): 35129–38. PMID10574995.
^Polissi A, Georgopoulos C (June 1996). "Mutational analysis and properties of the msbA gene of Escherichia coli, coding for an essential ABC family transporter". Mol. Microbiol.20 (6): 1221–33. PMID8809774.
^Zhou Z, White KA, Polissi A, Georgopoulos C, Raetz CR (May 1998). "Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid A and phospholipid biosynthesis". J. Biol. Chem.273 (20): 12466–75. doi:10.1074/jbc.273.20.12466. PMID9575204.