Insight on Bacterial Newborn Meningitis Using a Neurovascular-Unit-on-a-Chip

Rossana Rauti, Sharon Navok, Dvora Biran, Keshet Tadmor, Yael Leichtmann-Bardoogo, Eliora Z. Ron, Ben M. Maoz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Understanding the pathogenesis of bacterial infections is critical for combatting them. For some infections, animal models are inadequate and functional genomic studies are not possible. One example is bacterial meningitis, a life-threatening infection with high mortality and morbidity. Here, we used the newly developed, physiologically relevant, organ-on-a-chip platform integrating the endothelium with neurons, closely mimicking in vivo conditions. Using high-magnification microscopy, permeability measurements, electrophysiological recordings, and immunofluorescence staining, we studied the dynamic by which the pathogens cross the blood-brain barrier and damage the neurons. Our work opens up possibilities for performing large-scale screens with bacterial mutant libraries for identifying the virulence genes involved in meningitis and determining the role of these genes, including various capsule types, in the infection process. These data are essential for understanding and therapy of bacterial meningitis. Moreover, our system offers possibilities for the study of additional infections—bacterial, fungal, and viral. IMPORTANCE The interactions of newborn meningitis (NBM) with the neurovascular unit are very complex and are hard to study. This work presents a new platform to study NBM in a system that enables monitoring of multicellular interactions and identifies processes that were not observed before.

Original languageEnglish
JournalMicrobiology spectrum
Volume11
Issue number3
DOIs
StatePublished - May 2023

Funding

FundersFunder number
Aufzien Family Center for the Prevention and Treatment of Parkinson’s Disease at Tel Aviv University
European Research Council851765
Israel Science Foundation2248/19
Azrieli Foundation
Ministry of Science and Technology, Israel3-17351

    Keywords

    • BBB permeability
    • E. coli
    • KEYWORDS bacterial meningitis
    • MEA
    • electrophysiology
    • in vitro models
    • neuronal network
    • neurovascular unit
    • newborn meningitis
    • organ-on-a-chip
    • vascular cells

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