Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0085437 (
bacterial meningitis
)
4,038
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Elevated levels of pterins and nitric oxide (NO) are observed in patients with septic shock and
bacterial meningitis
. We demonstrate that Escherichia coli K1 infection of human brain microvascular endothelial cells (HBMECs) induces the expression of guanosine triphosphate cyclohydrolase (
GCH1
), the rate-limiting enzyme in pterin synthesis, thereby elevating levels of biopterin. DAHP (2,4-diamino hydroxyl pyrimidine), a specific inhibitor of
GCH1
, prevented biopterin and NO production and invasion of E. coli K1 in HBMECs.
GCH1
interaction with Ecgp96, the receptor for outer membrane protein A of E. coli K1, also increases on infection, and suppression of Ecgp96 expression prevents
GCH1
activation and biopterin synthesis. Pretreatment of newborn mice with DAHP prevented the production of biopterin and the development of meningitis. These results suggest a novel role for biopterin synthesis in the pathogenesis of E. coli K1 meningitis.
...
PMID:Attenuation of biopterin synthesis prevents Escherichia coli K1 invasion of brain endothelial cells and the development of meningitis in newborn mice. 2310 May 63
