Microbial cell membrane and associated negatively charged surface components

The microbial cell membrane and its associated negatively charged surface components, such as lipopolysaccharides (LPS) in Gram-negative bacteria and teichoic acids in Gram-positive bacteria, constitute a vital structural target for several classes of antibiotics (StatPearls, 2023). These components create an anionic surface environment that facilitates the initial electrostatic recruitment of cationic antimicrobial agents, including polymyxins and daptomycin (PubMed, PMID: 27547111). Once bound, these agents insert into the lipid bilayer, causing physical disruption, pore formation, or depolarization, which results in the loss of essential ions and metabolites (Nature Reviews Microbiology, 2017). This target is particularly significant in the treatment of carbapenem-resistant Enterobacteriaceae and other multi-drug resistant (MDR) pathogens where traditional metabolic targets are bypassed by resistance mechanisms. The physical nature of this target makes it difficult for microbes to develop resistance through simple point mutations, although modifications to surface charge (e.g., via the mcr-1 gene) can occur. However, the clinical utility of drugs hitting this target is often constrained by narrow therapeutic windows due to potential cross-reactivity with mammalian membranes, leading to adverse effects like nephrotoxicity and neurotoxicity (Journal of Antimicrobial Chemotherapy, 2019).

Other names

Bacterial cell membraneFungal cell membraneAnionic microbial surfaceNegatively charged microbial membraneMicrobial lipid bilayer

Electrostatic binding to anionic surface components followed by membrane insertion, pore formation, and physical disruption of the lipid bilayer leading to cytoplasmic leakage and cell death.