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A phytantriol-based cubosome formulation as an antimicrobial against lipopolysaccharide-deficient Gram-negative bacteria.

Treatment of multi-drug 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. The phytantriol-based cubosomes were highly bactericidal against polymyxin-resistant, lipopolysaccharide (LPS) deficient, Acinetobacter 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.