Evidence map›Paper›PMID 40696419›Full record

ArticleFluids and barriers of the CNS2025

Neisseria meningitidis regulates P-glycoprotein transporter activity in brain endothelial cells via sphingosine 1-phosphate receptor 1.

Fatemeh Nosratabadi, Leo M Endres, Fabian Schumacher, Heike Claus, Burkhard Kleuser, Brandon J Kim, Alexandra Schubert-Unkmeir

Abstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Fatemeh NosratabadiInstitute for Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany.
Leo M EndresInstitute for Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany.
Fabian SchumacherInstitute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Heike ClausInstitute for Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany.
Burkhard KleuserInstitute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Brandon J KimDepartment of Biological Sciences, University of Texas at Dallas, Richardson, TX, USA.
Alexandra Schubert-UnkmeirInstitute for Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany. alexandra.schubert-unkmeir@uni-wuerzburg.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe brain endothelial cells (BECs) are essential for protecting the central nervous system (CNS) from xenobiotics and pathogens, including Neisseria meningitidis, while maintaining CNS homeostasis through tight junction (TJ) proteins and specialized transporters. Among these, multidrug resistance (MDR) transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are pivotal in restricting the entry of neurotoxic substances. Although the impact of N. meningitidis infection on BBB TJ is well-documented, its effect on MDR transporters remains largely unexplored.

methodsWe employed induced pluripotent stem cell-derived brain-like endothelial cells (iBECs) as an in vitro BECs model due to their human-like morphology and expression of junctional proteins and MDR transporters. iBECs were exposed to various N. meningitidis strains, isogenic mutants, heat-inactivated bacteria, conditioned media, or purified capsule polysaccharide (CPS). P-gp and BCRP activities were assessed using intracellular accumulation assays with Rhodamine 123 and Chlorin e6, respectively, in the presence of P-gp inhibitors cyclosporin A and PSC833 and BCRP inhibitor Ko143. Gene expression and protein levels were determined by qPCR and western blotting, and sphingolipid quantification was performed via liquid chromatography tandem-mass spectrometry (LC-MS/MS).

resultsInfection of iBECs with N. meningitidis inhibited P-gp activity, whereas BCRP activity remained unaffected. P-gp inhibition occurred without changes in gene expression or protein abundance. Cells infected with N. meningitidis showed reduced efficacy of P-gp inhibitors, an effect not seen with the BCRP inhibitor Ko143. N. meningitidis CPS was identified as a key factor in modulating P-gp activity. Notably, the inhibitory effect of N. meningitidis on P-gp activity was blocked by a specific sphingosine 1-phosphate receptor 1 (S1PR

conclusionsThese findings demonstrate that N. meningitidis infection impairs P-gp function through S1PR

Indexed as

ATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Blood-Brain BarrierBrainEndothelial CellsNeisseria meningitidisSphingosine-1-Phosphate ReceptorsCells, CulturedHumansInduced Pluripotent Stem CellsATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2S1PR1 protein, humanSphingosine-1-Phosphate ReceptorsBrain endothelial cellsBreast cancer resistance proteinEfflux transporterNeisseria meningitidisP-glycoproteinSphingosine 1-phosphate receptor 1

Identifiers

PMID40696419
PMCPMC12285036

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.