TY - JOUR
T1 - Insight on Bacterial Newborn Meningitis Using a Neurovascular-Unit-on-a-Chip
AU - Rauti, Rossana
AU - Navok, Sharon
AU - Biran, Dvora
AU - Tadmor, Keshet
AU - Leichtmann-Bardoogo, Yael
AU - Ron, Eliora Z.
AU - Maoz, Ben M.
N1 - Publisher Copyright:
Copyright © 2023 Rauti et al.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - BBB permeability
KW - E. coli
KW - KEYWORDS bacterial meningitis
KW - MEA
KW - electrophysiology
KW - in vitro models
KW - neuronal network
KW - neurovascular unit
KW - newborn meningitis
KW - organ-on-a-chip
KW - vascular cells
UR - http://www.scopus.com/inward/record.url?scp=85163913793&partnerID=8YFLogxK
U2 - 10.1128/spectrum.01233-23
DO - 10.1128/spectrum.01233-23
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C2 - 37222614
AN - SCOPUS:85163913793
SN - 2165-0497
VL - 11
JO - Microbiology spectrum
JF - Microbiology spectrum
IS - 3
ER -