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

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.

• Authors: Subramanian Krishnan, Alexander C Chang, Brian M Stoltz, Nemani V Prasadarao
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 214 Issue 7 Pg. 1092-104 (10 01 2016) ISSN: 1537-6613 [Electronic] United States
• PMID: 27456707 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Chemical References

• Bacterial Outer Membrane Proteins
• GPATCH1 protein, human
• Glucose Transporter Type 1
• Nerve Tissue Proteins
• PPAR gamma
• Receptors, Cell Surface
• SLC2A1 protein, human
• OMPA outer membrane proteins

Topics

• Animals
• Animals, Newborn
• Bacterial Outer Membrane Proteins (metabolism)
• Blood-Brain Barrier (pathology)
• Cell Line
• Disease Models, Animal
• Down-Regulation
• Glucose Transporter Type 1 (analysis)
• Humans
• Infant, Newborn
• Infant, Newborn, Diseases (pathology)
• Meningitis, Escherichia coli (pathology)
• Mice
• Nerve Tissue Proteins (metabolism)
• PPAR gamma (analysis)
• Receptors, Cell Surface (metabolism)