Microenvironment Magnesium Overload Disrupts Bacterial Membrane Functions for the Central Nervous System Infection Treatment

Bacterial infections of the central nervous system (CNS) remain life-threatening disorders with high mortality, largely due to limited drug permeability across the blood–brain barrier and dose-dependent toxicities of conventional antimicrobials. Here, we report a two-dimensional magnesene nanosheet generated by low-temperature ultrasound exfoliation of magnesium crystals via selective activation of dislocations and slip systems. The resulting material releases abundant Mg2+ ions at the bacterial interface, inducing localized magnesium overload and mechanical disruption of membrane integrity. This dual physicochemical stress impairs membrane-associated transport in Staphylococcus aureus and Escherichia coli, ultimately triggering rapid bactericidal effects. Magnesene exhibits potent and broad-spectrum antimicrobial activity in vitro, and analysis of clinical cerebrospinal fluid samples from CNS-infected patients further confirms its translational potential in reducing microbial burden. In rat CNS infection models, magnesene markedly suppresses bacterial proliferation and attenuates neuroinflammation. As a novel inorganic nanomedicine, magnesene offers a promising strategy for combating refractory CNS infections and may broaden therapeutic options against diverse microbial pathogens.