Attenuation of biopterin synthesis prevents Escherichia coli K1 invasion of brain endothelial cells and the development of meningitis in newborn mice.
J Infect Dis
; 207(1): 61-71, 2013 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-23100563
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
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3_ND
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4_TD
Base de dados:
MEDLINE
Assunto principal:
Biopterinas
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Encéfalo
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Meningite devida a Escherichia coli
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Células Endoteliais
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Escherichia coli
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2013
Tipo de documento:
Article