Border Control: Regulating LPS Biogenesis

The outer membrane (OM) is a defining feature of Gram-negative bacteria that serves as a permeability barrier and provides rigidity to the cell. Critical to OM func-tion is establishing and maintaining an asymmetrical bilayer structure with phos-pholipids in the inner leaflet and the complex glycolipid lipopolysaccharide (LPS) in the outer leaflet. Cells ensure this asymmetry by regulating the biogenesis of lipid A, the conserved and essential anchor of LPS. Here we review the conse-quences of disrupting the regulatory components that control lipid A biogenesis, focusing on the rate-limiting step performed by LpxC. Dissection of these pro-cesses provides critical insights into bacterial physiology and potential new targets for antibiotics able to overcome rapidly spreading resistance mechanisms. Functions of Lipopolysaccharide Gram-negative bacteria are diderms, possessing both an inner membrane (IM) and an outer membrane (OM). These two membranes define a cellular compartment called the periplasm in which the peptidoglycan (PG) cell wall resides. The OM is unlike any other biological membrane. It is a lipid bilayer, but it is asymmetric. Phospholipids (PLs) make up the inner leaflet while the