Gram-negative bacterial outer membrane lipopolysaccharide and cytoplasmic membrane phospholipids (LPS/Phospholipids)

The Gram-negative bacterial outer membrane lipopolysaccharide (LPS) and cytoplasmic membrane phospholipids are essential structural components that define the cell envelope of Gram-negative bacteria [1]. LPS is a complex glycolipid found in the outer leaflet of the outer membrane, where it acts as a potent endotoxin and a critical permeability barrier against toxic molecules, including many antibiotics [3]. This structure is stabilized by divalent cations like magnesium and calcium that bridge the negatively charged phosphate groups of the lipid A moiety [6]. The cytoplasmic membrane, located beneath the peptidoglycan layer, consists of a phospholipid bilayer that regulates the transport of solutes and maintains the cell's energetic state [7]. Polymyxin antibiotics, such as polymyxin B and colistin, specifically target this system by displacing the stabilizing cations from LPS, leading to outer membrane disruption [8]. Following this initial interaction, the drugs insert into the cytoplasmic membrane phospholipids, creating pores that cause the leakage of essential intracellular contents and rapid bacterial death [2, 5]. Because of their unique mechanism, these components are vital targets for treating multidrug-resistant Gram-negative infections, although their use is often limited by significant side effects like nephrotoxicity [8].

Other names

Gram-negative bacterial cell envelopeBacterial outer and inner membranesLPS and phospholipidsBacterial cell membrane

Polymyxins act by binding to the lipid A portion of lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, displacing divalent cations (Mg2+ and Ca2+) that normally stabilize the LPS layer. This displacement destabilizes the outer membrane, allowing the drug to penetrate the periplasm and reach the cytoplasmic membrane. There, the drug inserts into the phospholipid bilayer, causing pore formation, leakage of intracellular contents, and ultimately bacterial cell death.