Abstract：
:Macrophages serve as permissive niches for Escherichia coli (E. coli) K1 to attain high grade bacteremia in the pathogenesis of meningitis in neonates. Although pterin levels are a diagnostic marker for immune activation, the role of macrophages in pterin production and in the establishment of meningitis is unknown. Here, we demonstrate that macrophages infected with E. coli K1 produce both neopterin and biopterin through increased expression of GTP-cyclohydrolase 1 (GCH1). Of note, increased production of biopterin enhances the expression of Fc-gamma receptor I (CD64), which in turn, aided the entry of E. coli K1 in macrophages while increased neopterin suppresses reactive oxygen species (ROS), thereby aiding bacterial survival. Inhibition of GCH1 by 2, 4-Diamino-6-hydroxypyrimidine (DAHP) prevented the E. coli K1 induced expression of CD64 in macrophages in vitro and the development of bacteremia in a newborn mouse model of meningitis. These studies suggest that targeting GCH1 could be therapeutic strategy for preventing neonatal meningitis by E. coli K1.
journal_name
Microbes Infectjournal_title
Microbes and infectionauthors
Shanmuganathan MV,Krishnan S,Fu X,Prasadarao NVdoi
10.1016/j.micinf.2013.10.013subject
Has Abstractpub_date
2014-02-01 00:00:00pages
134-41issue
2eissn
1286-4579issn
1769-714Xpii
S1286-4579(13)00215-3journal_volume
16pub_type
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