Synergistic Membrane Disturbance Improves the Antibacterial Performance of Polymyxin B

Drug-resistant Gram-negative bacteria pose a serious threat to public health, and polymyxin B (PMB) is clinically used as a last-line therapy for the treatment of infections caused by these pathogens. However, the appearance of PMB resistance calls for an effort to develop new approaches to improve its antibacterial performance. In this work, a new type of nanocomposite, composed of PMB molecules being chemically decorated on the surface of graphene oxide (GO) nanosheets, was designed, which showed potent antibacterial ability through synergistically and physically disturbing the bacterial membrane. The as-fabricated PMB@GO nanocomposites demonstrated an enhanced bacterial-killing efficiency, with a minimum inhibitory concentration (MIC) value half of that of free PMB (with an MIC value as low as 0.5 mu g mL(-1) over Escherichia coli), and a bacterial viability less than one fourth of that of PMB (with a bacterial reduction of 60% after 3 h treatment, and 90% after 6 h incubation). Furthermore, the nanocomposite displayed moderate cytotoxicity or hemolysis effect, with cellular viabilities over 85% at concentrations up to 16 times the MIC value. Studies on antibacterial mechanism revealed that the synergy between PMB molecules and GO nanosheets greatly facilitated the vertical insertion of the nanocomposite into the lipid membrane, leading to membrane disturbance and permeabilization. Our results demonstrate a physical mechanism for improving the antibacterial performance of PMB and developing advanced antibacterial agents for better clinic uses.

Automated summary

In this study, a new type of nanocomposite, composed of polymyxin B (PMB) molecules being chemically decorated on the surface of graphene oxide (GO) nanosheets, was designed to improve the antibacterial performance of PMB. The nanocomposite showed potent antibacterial ability by disturbing the bacterial membrane. The results demonstrate the potential of developing advanced antibacterial agents using this physical mechanism.