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- Title
Escherichia coli K1 Modulates Peroxisome Proliferator-Activated Receptor γ and Glucose Transporter 1 at the Blood-Brain Barrier in Neonatal Meningitis.
- Authors
Krishnan, Subramanian; Chang, Alexander C.; Stoltz, Brian M.; Prasadarao, Nemani V.
- Abstract
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 γ (PPAR-γ) 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-γ 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-γ agonists ameliorate the pathological outcomes of infection by suppressing interleukin 6 production in the brain. Thus, inhibition of PPAR-γ and GLUT-1 by E. coli K1 is a novel pathogenic mechanism in meningitis, and pharmacological upregulation of PPAR-γ and GLUT-1 levels may provide novel therapeutic avenues.
- Subjects
NEONATAL Escherichia coli infections; NEONATAL infections; MENINGITIS in children; BLOOD-brain barrier; GLUCOSE transporters; GLUCOKINASE; PEDIATRIC neurology; PROTEIN analysis; ANIMAL experimentation; ANIMAL populations; BIOCHEMISTRY; BIOLOGICAL models; CARRIER proteins; CELL lines; CELL receptors; NEONATAL diseases; PHENOMENOLOGY; MEMBRANE proteins; MICE; NERVE tissue proteins; RESEARCH funding; BACTERIAL meningitis
- Publication
Journal of Infectious Diseases, 2016, Vol 214, Issue 7, p1092
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw306