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Bacterial cell wall and surface anionic groups are essential structural components that provide a net negative charge to the bacterial surface. In Gram-positive bacteria, these primarily consist of teichoic acids (TA) and lipoteichoic acids (LTA), while in Gram-negative bacteria, the negative charge is largely attributed to the phosphate groups of lipopolysaccharides (LPS) (Swoboda et al., 2010, doi:10.1002/cbic.200900567). These anionic groups play critical roles in maintaining cell wall integrity, regulating ion homeostasis, and facilitating adhesion to host tissues (Silhavy et al., 2010, doi:10.1101/cshperspect.a000414). Because of their fundamental importance and accessibility on the cell exterior, they serve as primary targets for several classes of antibiotics, most notably the polymyxins and certain lipoglycopeptides (Yu et al., 2015, doi:10.3389/fmicb.2015.00311). Polymyxins, for instance, bind electrostatically to the lipid A component of LPS, disrupting the outer membrane of Gram-negative pathogens. Daptomycin utilizes a calcium-dependent mechanism to interact with anionic components in Gram-positive membranes, leading to rapid depolarization and cell death (Humphries et al., 2013, doi:10.1128/AAC.00705-13). Understanding these surface groups is vital for developing new antimicrobial strategies, especially as bacteria evolve resistance by modifying these anionic targets to reduce drug binding (Baron et al., 2016, doi:10.1016/j.ijantimicag.2016.06.005).
Cationic antimicrobial agents bind electrostatically to these anionic groups, displacing stabilizing divalent cations (Mg2+, Ca2+) and disrupting the structural integrity of the bacterial cell wall or membrane, leading to cell death.
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