Gram-negative bacterial outer and cytoplasmic membranes (OM/IM)

The Gram-negative bacterial cell envelope is a complex, multi-layered structure consisting of an inner (cytoplasmic) membrane, a thin peptidoglycan cell wall, and a unique outer membrane. The outer membrane serves as a formidable permeability barrier, containing lipopolysaccharides (LPS) that protect the bacteria from harsh environments and many antibiotics [1][3]. The cytoplasmic membrane is a phospholipid bilayer responsible for essential processes such as oxidative phosphorylation, nutrient transport, and lipid synthesis [3]. This dual-membrane system is a critical therapeutic target for several classes of antibiotics, most notably the polymyxins, which act as detergents to disrupt membrane integrity [2]. Targeting these membranes is essential for treating multi-drug resistant (MDR) infections caused by pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii. However, drug development is challenged by the need to penetrate the outer membrane while avoiding toxicity to host human cell membranes [1][2].

Other names

Gram-negative cell envelopeBacterial cell wall (Gram-negative)Outer membrane and inner membraneBacterial lipid bilayers

Disruption of membrane integrity through displacement of divalent cations (Mg2+ and Ca2+) from lipopolysaccharides (LPS), leading to increased permeability, pore formation, and osmotic lysis. Specific agents may also inhibit the assembly of outer membrane proteins (e.g., BamA or LptD) or disrupt phospholipid packing in the cytoplasmic membrane [1][2].