A polytherapy based approach to combat antimicrobial resistance using cubosomes
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Date
2022-01-17
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Nature
Abstract
A depleted antimicrobial drug pipeline combined with an increasing prevalence of Gram-negative ‘superbugs’ has increased interest in nano therapies to treat antibiotic resistance. As cubosomes and polymyxins disrupt the outer membrane of Gram-negative bacteria via different mechanisms, we herein examine the antimicrobial activity of polymyxin-loaded cubosomes and explore an alternative strategy via the polytherapy treatment of pathogens with cubosomes in combination with polymyxin. The polytherapy treatment substantially increases antimicrobial activity compared to polymyxin B-loaded cubosomes or polymyxin and cubosomes alone. Confocal microscopy and neutron reflectometry suggest the superior polytherapy activity is achieved via a two-step process. Firstly, electrostatic interactions between polymyxin and lipid A initially destabilize the outer membrane. Subsequently, an influx of cubosomes results in further membrane disruption via a lipid exchange process. These findings demonstrate that nanoparticle-based polytherapy treatments may potentially serve as improved alternatives to the conventional use of drug-loaded lipid nanoparticles for the treatment of “superbugs”. © The Authors - Open Access CC-BY 4.0
Description
Keywords
Antimicrobial agents, Drugs, Pathogens, Therapy, Microscopy, Neutron reflectors, Lipids, Membranes, Public health
Citation
Lai, X., Han, M.-L., Ding, Y., Chow, S. H., Le Brun, A. P., Wu, C.-M., Bergen, P. J., Jiang, J.-h., Hsu, H.-Y., Muir, B. W., White, J., Song, J., Li, J., & Shen, H.-H. (2022). A polytherapy based approach to combat antimicrobial resistance using cubosomes. Nature Communications, 13(1), 343.doi:10.1038/s41467-022-28012-5