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Microbial surface anionic molecules are a broad class of negatively charged structures located on the outer envelope of bacteria and fungi. In Gram-negative bacteria, the primary anionic component is lipopolysaccharide (LPS), which is anchored in the outer membrane (Sperandeo et al., 2017). Gram-positive bacteria possess teichoic and lipoteichoic acids (LTA) that extend through the peptidoglycan layer, providing a high density of negative charge (Swoboda et al., 2010). These molecules are critical for maintaining the structural integrity of the cell wall, regulating the passage of ions, and facilitating adherence to host tissues. Because mammalian cell membranes are largely composed of neutral zwitterionic lipids, these anionic surfaces serve as a selective target for the innate immune system and therapeutic agents (Zasloff, 2002). Cationic antimicrobial peptides (CAMPs) and drugs like polymyxins utilize electrostatic attraction to bind these anionic sites (Landman et al., 2008). This binding often leads to the displacement of stabilizing divalent cations, such as calcium and magnesium, resulting in membrane permeabilization and cell death. Targeting these molecules is a key strategy in developing treatments for multi-drug resistant infections, although it carries risks such as the release of endotoxins during microbial lysis.
Drugs target these molecules through electrostatic interactions between their cationic groups and the anionic phosphate or carboxyl groups of the microbial surface (Zasloff, 2002). This binding displaces stabilizing divalent cations such as magnesium and calcium, leading to membrane disruption, pore formation, and eventual cell lysis (Landman et al., 2008).
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