Phytantriol-based cubosome formulation as an antimicrobial against lipopolysaccharide-deficient gram-negative bacteria

Xiangfeng Lai, Yue Ding, Chun-Ming Wu, Xiaoyu Chen, Jhih-hang Jiang, Hsien-Yi Hsu, Yajun Wang, Anton P. Le Brun, Jiangning Song, Mei-Ling Han, Jian Li, Hsin-Hui Shen

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Treatment of multidrug-resistant (MDR) bacterial infections increasingly relies on last-line antibiotics, such as polymyxins, with the urgent need for discovery of new antimicrobials. Nanotechnology-based antimicrobials have gained significant importance to prevent the catastrophic emergence of MDR over the past decade. In this study, phytantriol-based nanoparticles, named cubosomes, were prepared and examined in vitro by minimum inhibitory concentration (MIC) and time-kill assays against Gram-negative bacteria: Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Phytantriol-based cubosomes were highly bactericidal against polymyxin-resistant, lipopolysaccharide (LPS)-deficient A. baumannii strains. Small-angle neutron scattering (SANS) was employed to understand the structural changes in biomimetic membranes that replicate the composition of these LPS-deficient strains upon treatment with cubosomes. Additionally, to further understand the membrane–cubosome interface, neutron reflectivity (NR) was used to investigate the interaction of cubosomes with model bacterial membranes on a solid support. These results reveal that cubosomes might be a new strategy for combating LPS-deficient Gram-negative pathogens.
Original languageEnglish
Pages (from-to)44485–44498
Number of pages14
JournalACS Applied Materials & Interfaces
Volume12
Issue number40
DOIs
Publication statusPublished - 7 Oct 2020

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