Negatively charged microbial cytoplasmic membrane

The negatively charged microbial cytoplasmic membrane is a fundamental structural component of bacteria and fungi, serving as a semi-permeable barrier that regulates the transport of ions and nutrients (Epand & Epand, 2009, Biochimica et Biophysica Acta). Unlike mammalian cell membranes, which are predominantly composed of neutral zwitterionic lipids like phosphatidylcholine, microbial membranes are enriched with anionic phospholipids such as phosphatidylglycerol and cardiolipin (Malanovic & Lohner, 2016, Pharmaceuticals). This net negative charge creates a significant electrostatic gradient that is exploited by various antimicrobial agents, particularly cationic antimicrobial peptides (AMPs) and lipopeptides like daptomycin (Brogden, 2005, Nature Reviews Microbiology). Upon binding, these agents insert into the lipid bilayer, leading to the formation of pores or the general disruption of membrane integrity (Yeaman & Yount, 2003, Pharmacological Reviews). This disruption results in the dissipation of the transmembrane electrochemical gradient, also known as the proton motive force, leakage of essential cytoplasmic components, and rapid cell death. Because the membrane is essential for microbial survival and its composition differs significantly from host cells, it represents a high-value target for overcoming antibiotic resistance in clinical settings.

Other names

Bacterial cytoplasmic membraneBacterial inner membraneAnionic microbial membraneMicrobial plasma membrane

Cationic antimicrobial agents bind to anionic phospholipids (e.g., phosphatidylglycerol) via electrostatic interactions, followed by hydrophobic insertion into the bilayer. This leads to membrane permeabilization through mechanisms such as the barrel-stave, toroidal pore, or carpet models, causing depolarization and leakage of intracellular contents (Yeaman & Yount, 2003, Pharmacological Reviews; Malanovic & Lohner, 2016, Pharmaceuticals).