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

Bradley Joseph Whitehead; Fabio  Antennuci; Anders Toftegaard Boysen; Peter Lindberg Nejsum

doi:10.1038/s41429-023-00615-0

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

Bradley Joseph Whitehead^*, Fabio Antennuci, Anders Toftegaard Boysen, Peter Lindberg Nejsum^*

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin - Infektionssygdomme

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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.

Originalsprog	Engelsk
Tidsskrift	The Journal of Antibiotics
Vol/bind	76
Nummer	6
Sider (fra-til)	360–364
Antal sider	5
ISSN	0021-8820
DOI	https://doi.org/10.1038/s41429-023-00615-0
Status	Udgivet - jun. 2023

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10.1038/s41429-023-00615-0

Citationsformater

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

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.",

author = "Whitehead, {Bradley Joseph} and Fabio Antennuci and Boysen, {Anders Toftegaard} and Nejsum, {Peter Lindberg}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to the Japan Antibiotics Research Association.",

year = "2023",

month = jun,

doi = "10.1038/s41429-023-00615-0",

language = "English",

volume = "76",

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journal = "The Journal of Antibiotics",

issn = "0021-8820",

publisher = "Nature Publishing Group",

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Polymyxin B inhibits pro-inflammatory effects of E. coli outer membrane vesicles whilst increasing immune cell uptake and clearance. / Whitehead, Bradley Joseph; Antennuci, Fabio ; Boysen, Anders Toftegaard et al.
I: The Journal of Antibiotics, Bind 76, Nr. 6, 06.2023, s. 360–364.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Polymyxin B inhibits pro-inflammatory effects of E. coli outer membrane vesicles whilst increasing immune cell uptake and clearance

AU - Whitehead, Bradley Joseph

AU - Antennuci, Fabio

AU - Boysen, Anders Toftegaard

AU - Nejsum, Peter Lindberg

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

U2 - 10.1038/s41429-023-00615-0

DO - 10.1038/s41429-023-00615-0

M3 - Journal article

C2 - 37016014

SN - 0021-8820

VL - 76

SP - 360

EP - 364

JO - The Journal of Antibiotics

JF - The Journal of Antibiotics

IS - 6

ER -

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

Abstract

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