Escherichia coli K1 Modulates Peroxisome Proliferator-Activated Receptor {gamma} and Glucose Transporter 1 at the Blood-Brain Barrier in Neonatal Meningitis

Escherichia coli K1 meningitis continues to be a major threat to neonatal health. Previous studies demonstrated that outer membrane protein A (OmpA) of E. coli K1 interacts with endothelial cell glycoprotein 96 (Ecgp96) in the blood-brain barrier to enter the central nervous system. Here we show that the interaction between OmpA and Ecgp96 downregulates peroxisome proliferator–activated receptor (PPAR-) and glucose transporter 1 (GLUT-1) levels in human brain microvascular endothelial cells, causing disruption of barrier integrity and inhibition of glucose uptake. The suppression of PPAR- and GLUT-1 by the bacteria in the brain microvessels of newborn mice causes extensive pathophysiology owing to interleukin 6 production. Pretreatment with partial or selective PPAR- agonists ameliorate the pathological outcomes of infection by suppressing interleukin 6 production in the brain. Thus, inhibition of PPAR- and GLUT-1 by E. coli K1 is a novel pathogenic mechanism in meningitis, and pharmacological upregulation of PPAR- and GLUT-1 levels may provide novel therapeutic avenues.
Source: The Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: BACTERIA Source Type: research