Activation of brain endothelium by Escherichia coli K1 virulence factor cglD promotes polymorphonuclear leukocyte transendothelial migration

Medical Microbiology and Immunology
Ke ZhangYu-Hua Chen

Abstract

Escherichia coli K1 is the most common Gram-negative bacteria causing neonatal meningitis. Polymorphonuclear leukocyte (PMN) transmigration across the blood-brain barrier (BBB) is the hallmark of bacterial meningitis. Reportedly, the deletion of virulence factor cglD (E44:ΔcglD) from E44 is responsible for a less efficient PMN transendothelial migration ability. In the present study, we found that complementation of the cglD gene into E44:ΔcglD mutant strain might restore the PMN count and myeloperoxidase level in a neonatal mouse meningitis. Using human brain microvascular endothelial cells (HBMECs), the main model of the BBB in vitro, we found that E44:ΔcglD mutant strain induced a less efficient PMN adhesion to HBMECs and down-regulated chemokines CXCL1, CXCL6 and CXCL8 and adhesion molecule E-selectin, compared with the E44 strain. Complementation of cglD restored the PMN adhesion to HBMECs and the level of these proteins. E44:ΔcglD mutant strain also induced a less efficient NF-κB pathway activation in HBMECs and reduced the soluble p65 (sp65) level in the cerebral spinal fluid of newborn mice, compared with the E44 strain. Complementation of cglD restored the NF-κB pathway activation and increased the sp65 levels. This su...Continue Reading

References

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Oct 16, 2015·Einstein·Diana Carolina Torres Palomino, Luciana Cavalheiro Marti

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Citations

Nov 2, 2019·International Journal of Molecular Sciences·Rosanna HeroldChristian Schwerk

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Methods Mentioned

BETA
electrophoresis
enzyme-linked immunosorbent assay
Assay
nuclear translocation
ELISA
confocal microscopy
ubiquitination

Software Mentioned

Multi Gauge
SPSS

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