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Negatively charged microbial cell membranes and wound components serve as the primary site of action for many cationic antimicrobial agents. Bacterial surfaces are characterized by a high density of anionic molecules, such as lipopolysaccharides (LPS) in Gram-negative bacteria and teichoic acids in Gram-positive bacteria, which distinguish them from the relatively neutral surfaces of mammalian cells (Zasloff, 2002, Nature). In chronic wounds, this target extends to the extracellular polymeric substances (EPS) of biofilms, including negatively charged extracellular DNA and proteins that protect pathogens from the immune system (Flemming & Wingender, 2010, Nature Reviews Microbiology). Therapeutic agents like polymyxins and antimicrobial peptides (AMPs) bind to these anionic sites via electrostatic interactions, leading to membrane displacement, pore formation, and the eventual lysis of the microbe (Mahlapuu et al., 2016, Frontiers in Cellular and Infection Microbiology). Additionally, targeting these components in wounds helps to neutralize inhibitory factors that stall the healing process (Moore & Gray, 2007, Journal of Wound Care). This target is central to the development of membrane-active antibiotics that aim to circumvent traditional resistance mechanisms.
Electrostatic binding to anionic sites followed by physical disruption of the lipid bilayer or sequestration of inhibitory biofilm components.
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