Graphene oxide as antibacterial sensitizer: Mechanically disturbed cell membrane for enhanced poration efficiency of melittin

Natural antimicrobial peptides (AMPs) promise a fundamental solution to the devastating threat of multidrug-resistant bacteria, while drawbacks such as limited antibacterial efficiency block their clinical use. A key for solution is to enhance the bacterial membrane disruption ability of AMPs at low concentrations. Here, it was found that a small amount of graphene oxide (GO) nanosheets could have a strong effect on sensitizing lipid membranes to the peptide melittin and extremely decrease the required threshold concentration of melittin for killing of bacteria. Molecular leakage tests from model vesicles showed that pretreatment of membrane with GO, even at a low concentration of 0.1 μg mL−1, decreased the threshold working concentration of melittin to less than half of the initial value, while in the living bacteria tests, such sensitizing effect of GO reduced the MIC value of melittin by almost 10 times. By combining experiments and simulations, we found that the sensitizing effect of GO was derived from its similar mechanical disturbance to cell membranes as that of melittin at high concentrations in membrane structures including lipid diffusion, packing state, and pressure distribution. Our results provide a cost-effective strategy to enhance the antibacterial efficiency of AMPs for clinical use.