Polysaccharide‐targeting lipid nanoparticles to kill gram‐negative bacteria

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dc.contributor.authorLai, XFen_AU
dc.contributor.authorChow, SHen_AU
dc.contributor.authorLe Brun, APen_AU
dc.contributor.authorMuir, BWen_AU
dc.contributor.authorBergen, PJen_AU
dc.contributor.authorWhite, JFen_AU
dc.contributor.authorYu, HHen_AU
dc.contributor.authorWang, JPen_AU
dc.contributor.authorDanne, Jen_AU
dc.contributor.authorJiang, JHen_AU
dc.contributor.authorShort, FLen_AU
dc.contributor.authorHan, MLen_AU
dc.contributor.authorStrugnell, RAen_AU
dc.contributor.authorSong, JNen_AU
dc.contributor.authorCameron, NRen_AU
dc.contributor.authorPeleg, AYen_AU
dc.contributor.authorLi, Jen_AU
dc.contributor.authorShen, HHen_AU
dc.date.accessioned2025-03-11T02:56:55Zen_AU
dc.date.available2025-03-11T02:56:55Zen_AU
dc.date.issued2023-10-05en_AU
dc.date.statistics2025-03-11en_AU
dc.description.abstractThe rapid increase and spread of Gram‐negative bacteria resistant to many or all existing treatments threaten a return to the preantibiotic era. The presence of bacterial polysaccharides that impede the penetration of many antimicrobials and protect them from the innate immune system contributes to resistance and pathogenicity. No currently approved antibiotics target the polysaccharide regions of microbes. Here, describe monolaurin‐based niosomes, the first lipid nanoparticles that can eliminate bacterial polysaccharides from hypervirulent Klebsiella pneumoniae, are described. Their combination with polymyxin B shows no cytotoxicity in vitro and is highly effective in combating K. pneumoniae infection in vivo. Comprehensive mechanistic studies have revealed that antimicrobial activity proceeds via a multimodal mechanism. Initially, lipid nanoparticles disrupt polysaccharides, then outer and inner membranes are destabilized and destroyed by polymyxin B, resulting in synergistic cell lysis. This novel lipidic nanoparticle system shows tremendous promise as a highly effective antimicrobial treatment targeting multidrug‐resistant Gram‐negative pathogens. © 2023 The Authors. Published by Wiley-VCH GmbH2305052en_AU
dc.description.sponsorshipThe authors thank Ke Chen and Fang Lin for their assistance with the animal experiment, Jinxin Zhao and Hasini Wickremasinghe for their assistance with in vitro experiments. The authors thank Dianna Hocking for subculturing K. pneumoniae B5055 mutant strains (ΔwaaL, Δwza-cΔwaaF, ΔmsbB/lpxM, ΔompW, and KPN_01295) and Simon Crawford and Gediminas Gervinskas for support and discussion of electron microscopy. The authors gratefully acknowledge the use of the facilities at the Monash X-ray Platform and the Ramaciotti Centre for Cryo-Electron Microscopy (Monash University, Victoria, Australia). The Australian Nuclear Science and Technology Organization (ANSTO) is gratefully acknowledged for providing the neutron research facilities (proposal numbers P9149, P9095, P9665, and P13842). H.-H.S. is an Australian NHMRC Career Development Research Fellow (GNT1106798) and J.L. is an NHMRC Principal Research Fellow (APP1157909). This work was supported by the NHMRC project grant APP1144652. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians.en_AU
dc.format.mediumPrint-Electronicen_AU
dc.identifier.articlenumbere2305052en_AU
dc.identifier.citationLai, X., Chow, S. H., Le Brun, A. P., Muir, B. W., Bergen, P. J., White, J., Yu, H. H., Wang, J., Danne, J., Jiang, J.-h., Short, F. L., Han, M.-L., Strugnell, R. A., Song, J., Cameron, N. R., Peleg, A. Y., Li, J., & Shen, H.-H. (2024). Polysaccharide‐targeting lipid nanoparticles to kill gram‐negative bacteria. Small, 20(6), 2305052. doi:10.1002/smll.202305052en_AU
dc.identifier.issn1613-6810en_AU
dc.identifier.issn1613-6829en_AU
dc.identifier.issue6en_AU
dc.identifier.journaltitleSmallen_AU
dc.identifier.urihttp://dx.doi.org/10.1002/smll.202305052en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/16038en_AU
dc.identifier.volume20en_AU
dc.languageEnglishen_AU
dc.language.isoenen_AU
dc.publisherWileyen_AU
dc.subjectPolysaccharidesen_AU
dc.subjectLipidsen_AU
dc.subjectBacteriaen_AU
dc.subjectAntimicrobial agentsen_AU
dc.subjectIn vivoen_AU
dc.subjectPathogensen_AU
dc.subjectNanoparticlesen_AU
dc.titlePolysaccharide‐targeting lipid nanoparticles to kill gram‐negative bacteriaen_AU
dc.typeJournal Articleen_AU
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