Negatively charged microbial cell surface

The negatively charged microbial cell surface is a fundamental structural target for cationic antimicrobial agents, including polymyxins and antimicrobial peptides (AMPs). This negative charge is primarily generated by lipopolysaccharides (LPS) in Gram-negative bacteria and teichoic acids in Gram-positive bacteria, which create an electrostatic gradient that attracts positively charged molecules [1, 4]. Unlike mammalian cell membranes, which are largely zwitterionic and contain cholesterol, microbial surfaces provide a selective docking site for these cationic drugs [2]. Upon binding, the drugs displace stabilizing divalent cations and insert into the lipid bilayer, leading to membrane permeabilization and cell death [1, 3]. This target is highly significant in treating multi-drug resistant infections because it relies on broad physicochemical properties rather than a single protein binding site [2, 5]. However, pathogens can develop resistance by modifying their surface charge to reduce drug affinity [5].

Other names

Anionic microbial membraneBacterial cell surfaceMicrobial envelopeAnionic cell wall components

Cationic antimicrobial agents target the negatively charged microbial cell surface through initial electrostatic recruitment to anionic components like lipopolysaccharides or teichoic acids. This interaction leads to the displacement of membrane-stabilizing magnesium and calcium ions, followed by the hydrophobic insertion of the drug into the membrane. This process disrupts the lipid bilayer integrity via mechanisms such as the barrel-stave, toroidal pore, or carpet models, ultimately causing cytoplasmic leakage and rapid microbial lysis [1, 2, 4].