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Polymyxin B inhibits pro-inflammatory effects of E. coli outer membrane vesicles whilst increasing immune cell uptake and clearance

The Journal of Antibiotics volume 76, pages 360–364 (2023)Cite this article

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Abstract

Polymyxin B (PMB) is a peptide based antibiotic that binds the lipid A moiety of lipopolysaccharide (LPS) with a resultant bactericidal effect. The interaction of PMB with LPS presented on outer membrane vesicles (OMVs) is not fully known, however, a sacrificial role of OMVs in protecting bacterial cells by sequestering PMB has been described. Here we assess the ability of PMB to neutralize the immune-stimulatory properties of OMVs whilst modulating the uptake of OMVs in human immune cells. We show for the first time that PMB increases immune cell uptake of Escherichia coli derived OMVs whilst inhibiting TNF and IL-1β production. Therefore, we present a potential new role for PMB in the neutralization of OMVs via LPS masking and increased immune cell uptake.

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Acknowledgements

This work was supported by the Danish Council for Independent Research (DFF-1032-00242B).

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Authors and Affiliations

  1. Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark

    Bradley Whitehead, Anders T. Boysen & Peter Nejsum

  2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Bradley Whitehead, Anders T. Boysen & Peter Nejsum

  3. Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Fabio Antennuci

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  1. Bradley Whitehead
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Correspondence to Bradley Whitehead or Peter Nejsum.

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Whitehead, B., Antennuci, F., Boysen, A.T. et al. Polymyxin B inhibits pro-inflammatory effects of E. coli outer membrane vesicles whilst increasing immune cell uptake and clearance. J Antibiot 76, 360–364 (2023). https://doi.org/10.1038/s41429-023-00615-0

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