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Gram-negative bacterial membrane phospholipids are essential structural components of both the inner and outer membranes of Gram-negative bacteria. The primary phospholipids include phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL), which maintain the structural integrity and selective permeability of the cell envelope (Sohlenkamp & Geiger, 2016). In the outer membrane, these lipids are primarily located in the inner leaflet, while the outer leaflet is composed of lipopolysaccharides. These phospholipids serve as critical therapeutic targets for certain classes of antibiotics, most notably the polymyxins, which bind to the negatively charged lipid headgroups (Poirel et al., 2017). This binding disrupts the membrane's stability, leading to leakage of intracellular contents and rapid bacterial lysis (Trimble et al., 2016). Because these lipids are fundamental to bacterial survival and differ in composition from eukaryotic membranes, they provide a basis for selective toxicity, although high doses can lead to significant side effects in humans.
Polymyxins act by binding to the negatively charged phosphate groups of phospholipids and lipopolysaccharides in the bacterial membranes. This interaction displaces divalent cations (calcium and magnesium) that stabilize the membrane, leading to increased permeability, membrane disruption, and cell death (Poirel et al., 2017).
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