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Published on: September 29, 2019
Polymyxin B inhibits pro-inflammatory effects of E. coli outer membrane vesicles whilst increasing immune cell uptake
Bradley Whitehead1,2, Fabio Antennuci3, Anders T Boysen4,5
1Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark. bradley@clin.au.dk.
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.
Insights
Polymyxin B (PMB) antibiotic neutralizes bacterial outer membrane vesicles (OMVs) by masking their lipopolysaccharide (LPS). This process enhances immune cell uptake of OMVs while reducing inflammatory cytokine production.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Polymyxin B (PMB) is a peptide antibiotic targeting bacterial lipopolysaccharide (LPS).
- Outer membrane vesicles (OMVs) can sequester PMB, potentially protecting bacteria.
- The interaction between PMB and OMVs and its effect on immune responses are not fully understood.
Purpose of the Study:
- To investigate how PMB affects the immune-stimulatory properties of Escherichia coli OMVs.
- To determine if PMB modulates the uptake of OMVs by human immune cells.
Main Methods:
- Assessing PMB's ability to neutralize immune-stimulatory properties of OMVs.
- Modulating the uptake of OMVs in human immune cells with PMB.
- Measuring TNF and IL-1β production.
Main Results:
- PMB increases the uptake of E. coli OMVs by human immune cells.
- PMB inhibits the production of inflammatory cytokines TNF and IL-1β in response to OMVs.
- LPS masking by PMB is suggested as a mechanism for altered OMV-host interaction.
Conclusions:
- PMB exhibits a novel role in neutralizing OMVs.
- PMB enhances immune cell uptake of OMVs.
- PMB may serve as a therapeutic agent to modulate OMV-induced inflammation.
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