Phytantriol-Based Cubosome Formulation as an Antimicrobial against Lipopolysaccharide-Deficient Gram-Negative Bacteria

  • ACS Appl Mater Interfaces. 2020 Oct 7;12(40):44485-44498. doi: 10.1021/acsami.0c13309.
Xiangfeng Lai  1 ,  Yue Ding  1  2 ,  Chun-Ming Wu  3  4 ,  Xiaoyu Chen  1 ,  Jhih-Hang Jiang  5 ,  Hsien-Yi Hsu  6  7 ,  Yajun Wang  8 ,  Anton P Le Brun  3 ,  Jiangning Song  2 ,  Mei-Ling Han  5 ,  Jian Li  5 ,  Hsin-Hui Shen  1  2
Affiliations
  • 1. Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, Victoria 3800, Australia.
  • 2. Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
  • 3. Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
  • 4. National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.
  • 5. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.
  • 6. School of Energy and Environment & Department of Materials Science and Engineering, City University of Hong Kong, Kowloon Tong, Hong Kong, China.
  • 7. Shenzhen Research Institute of City University of Hong Kong, Shenzhen 518057, China.
  • 8. College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325027, Zhejiang, China.
PMID: 32942850 DOI: 10.1021/acsami.0c13309
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.

Keywords
antimicrobials; cubosomes; lipopolysaccharide-deficient; multidrug resistance; outer membrane.
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