Engineered Graphene Oxide Nanocomposite Capable of Preventing the Evolution of Antimicrobial Resistance

Antimicrobial resistance (AMR) is spreading worldwide and keeps evolving to adapt to antibiotics, causing increasing threats in clinics, which necessitates the exploration of antimicrobial agents for not only killing of resistant cells but also prevention of AMR progression. However, so far, there has been no effective approach. Herein, we designed lanthanum hydroxide and graphene oxide nanocomposites (La@GO) to confer synergistic bactericidal effect in all tested resistant strains. More importantly, long-term exposure of E. coli (AMR) to sub-minimum inhibitory concentrations of La@GO does not trigger detectable secondary resistance, while the conventional antibiotic and silver nanoparticles lead to 16- to 64-fold increase in tolerance. The inability of E. coli to evolve resistance to La@GO is likely due to a distinctive extracellular multi-target invasion killing mechanism involving lipid dephosphorylation, lipid peroxidation and peptidoglycan disruption. Overall, our results highlight La@GO nanocomposit...