Divalent cations in bacterial outer membrane components

Divalent cations, primarily magnesium (Mg2+) and calcium (Ca2+), serve as essential structural anchors within the outer membrane of Gram-negative bacteria (Nikaido, H., 2003, Microbiology and Molecular Biology Reviews). These ions function by electrostatically bridging the negatively charged phosphate groups of adjacent lipopolysaccharide (LPS) molecules, which neutralizes repulsive forces and stabilizes the membrane lattice (Clifton, L. A., et al., 2015, Angewandte Chemie). This ionic cross-linking is critical for maintaining a robust permeability barrier that protects the cell from detergents, host immune factors, and various antibiotics. Therapeutic agents such as polymyxins (e.g., Colistin and Polymyxin B) target this site by competitively displacing the divalent cations due to their higher polycationic affinity for the LPS phosphates (Trimble, M. J., et al., 2007, Cold Spring Harbor Perspectives in Medicine). The resulting displacement causes localized membrane cracks and increased permeability, eventually leading to cell lysis and death. Additionally, chelating agents like EDTA can sequester these cations, sensitizing bacteria to other antimicrobial agents by compromising the outer membrane's integrity (Vaara, M., 1992, Microbiological Reviews).

Other names

LPS-stabilizing divalent cationsOuter membrane magnesium and calcium ionsLipopolysaccharide-divalent cation complexOuter membrane ionic bridges

Competitive displacement of divalent cations from lipopolysaccharide phosphate groups, leading to outer membrane disruption and increased permeability (Trimble, M. J., et al., 2007).