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Published on: April 18, 2019
Synergistic Membrane Disturbance Improves the Antibacterial Performance of Polymyxin B
Wenwen Li1,2, Che Zhang1,2, Xuemei Lu3
1Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China.
Abstract:
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 μg 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.
Insights
Drug-resistant bacteria are a major threat. Researchers developed a new polymyxin B-graphene oxide nanocomposite that enhances antibacterial activity and reduces toxicity, offering a promising alternative for treating resistant infections.
Area of Science:
- Materials Science
- Biotechnology
- Infectious Diseases
Background:
- Drug-resistant Gram-negative bacteria present a significant global health challenge.
- Polymyxin B (PMB) is a critical last-line antibiotic, but resistance is emerging.
- Novel strategies are needed to enhance PMB efficacy and overcome resistance.
Purpose of the Study:
- To design and evaluate a novel polymyxin B-graphene oxide (PMB@GO) nanocomposite.
- To investigate the synergistic antibacterial mechanism of the PMB@GO nanocomposite.
- To assess the therapeutic potential of PMB@GO against drug-resistant bacteria.
Main Methods:
- Chemical decoration of PMB molecules onto graphene oxide (GO) nanosheets.
- Determination of minimum inhibitory concentration (MIC) and bacterial viability assays.
- Cytotoxicity and hemolysis assays.
- Investigation of the antibacterial mechanism via membrane interaction studies.
Main Results:
- PMB@GO nanocomposites exhibited significantly enhanced antibacterial activity compared to free PMB, with a 2-fold lower MIC against *Escherichia coli*.
- Bacterial viability was reduced to less than one fourth with PMB@GO treatment compared to PMB alone.
- The nanocomposite demonstrated low cytotoxicity and hemolysis, with over 85% cellular viability at 16 times the MIC.
- Synergistic interaction between PMB and GO facilitated membrane insertion and disruption.
Conclusions:
- The developed PMB@GO nanocomposite offers a potent strategy to improve PMB's antibacterial performance through a physical membrane disturbance mechanism.
- This approach shows promise for developing advanced antibacterial agents to combat drug-resistant Gram-negative bacterial infections.
- PMB@GO represents a viable alternative for clinical applications requiring enhanced efficacy and reduced toxicity.
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