Gram-negative bacterial cell envelope

The Gram-negative bacterial cell envelope is a complex, multi-layered structure comprising an inner cytoplasmic membrane (IM), a periplasmic space containing a thin peptidoglycan layer, and an asymmetric outer membrane (OM) (Silhavy et al., 2010, Cold Spring Harb Perspect Biol). The OM is uniquely characterized by the presence of lipopolysaccharides (LPS) in its outer leaflet, which functions as a potent permeability barrier against toxic compounds, including many antibiotics (Nikaido, 2003, Microbiol Mol Biol Rev). This envelope serves as a critical therapeutic target; for example, polymyxins (colistin and polymyxin B) interact with the lipid A portion of LPS to disrupt membrane integrity, leading to cell death (Zheng et al., 2023, Nat Commun). Additionally, the synthesis of the peptidoglycan layer within the periplasm is the target of beta-lactam antibiotics, which inhibit penicillin-binding proteins (PBPs) (Bush & Bradford, 2016, Cold Spring Harb Perspect Med). Targeting these components is essential for treating infections caused by multi-drug resistant pathogens, though challenges include the emergence of resistance mechanisms like efflux pumps and modified LPS (Breijyeh et al., 2020, Molecules). The structural complexity of these membranes remains a significant hurdle in antibiotic discovery, requiring agents to bypass the OM to reach targets in the periplasm or cytoplasm. Furthermore, the release of endotoxins during membrane disruption can trigger severe systemic inflammatory responses in patients.

Other names

Gram-negative bacterial membranesOuter and inner bacterial membranesBacterial cell envelopeGram-negative cell wall

Disruption of membrane integrity through binding to lipopolysaccharides (LPS), displacement of divalent cations, inhibition of peptidoglycan biosynthesis, and interference with membrane-bound transport systems.