A research team has developed a new non-antibiotic strategy to treat central nervous system (CNS) bacterial infections using two-dimensional magnesene nanosheets that kill bacteria through a “localized magnesium overload” mechanism. The work was published in the Journal ofthe American Chemical Society.

The study was led by Prof. Jianlin SHI and Prof. Han LIN from the Shanghai Institute of Ceramics, Chinese Academy of Sciences (SICCAS), in collaboration with Prof. Rong XIE from Huashan Hospital, Fudan University.

Unlike conventional antibiotics that target bacterial proteins or metabolic pathways, magnesene nanosheets preferentially adhere to bacterial membranes through electrostatic interactions. Once attached, they continuously release magnesium ions (Mg²⁺) at the bacteria-material interface, creating a localized magnesium-rich microenvironment rather than a uniform increase in extracellular magnesium concentration.

This localized magnesium overload severely disrupts bacterial membrane ion balance and transmembrane transport. In particular, magnesene significantly inhibits glucose uptake and bacterial energy metabolism by interfering with the phosphotransferase system, ultimately leading to membrane dysfunction and bacterial death. This antibacterial mechanism is fundamentally different from traditional reactive oxygen species-mediated killing or antibiotic inhibition, representing a new ion-dysregulation-based strategy.

To validate this mechanism, the team combined zeta potential analysis, magnesium ion fluorescence imaging, ICP quantification, electron microscopy, and molecular dynamics simulations. The results showed strong adhesion between magnesene and bacterial membranes, pronounced magnesium enrichment at the bacterial surface, and severe membrane disruption caused by the sharp edges of the two-dimensional nanosheets.

Both in vitro and in vivo experiments confirmed the potent antibacterial activity of magnesene against methicillin-resistant Staphylococcus aureus (MRSA), a common multidrug-resistant bacterium. In a rat CNS infection model, magnesene markedly reduced bacterial burden in brain and spinal cord tissues, showing therapeutic efficacy comparable to vancomycin—a standard antibiotic—while exhibiting minimal liver and kidney toxicity.

CNS bacterial infections remain a major clinical challenge due to the limited ability of antibiotics to cross the blood-brain barrier and the increasing emergence of drug-resistant bacteria. Conventional antibiotic therapies are often associated with poor efficacy and significant side effects. This work establishes a previously unrecognized antibacterial paradigm based on localized ionic dysregulation and provides a promising non-antibiotic strategy for treating multidrug-resistant CNS bacterial infections.

Structural, simulation, and membrane damage analyses reveal magnesene's preferential interfacial interaction and mechanical disruption mechanism on bacterial membranes.

Contact: LIN Han

Shanghai Institute of Ceramics Chinese Academy of Sciences

E-mail: linhan@mail.sic.ac.cn

Published online: May 14, 2026