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Volume 49, Number 6, December 2016

Recombinant OmpA protein fragments mediate interleukin-17 regulation to prevent Escherichia coli meningitis 


Wen-Shyang Hsieh, Yi-Yuan Yang, Pei-Hsuan Lin, Chia-Chih Chang, Hsueh-Hsia Wu


 

Corresponding author:

Hsueh-Hsia Wu 



 

Background and purpose: 

Neonates are at a higher risk for bacterial meningitis than children of other age groups. Although the mortality rates have decreased over the past few decades, neonatal meningitis is still a severe disease with high morbidity. For bacterial meningitis, antibiotic therapy is the primary choice for management. However, neurologic complications often cannot be averted; ∼40% of survivors exhibit neurological sequelae. Escherichia coli infection is the common cause of neonatal meningitis. Previously, we have demonstrated that the recombinant loop 1–3, loop 2–3, and loop 2–4 fragments of OmpA protein can protect mice from death after intracerebral E. coli infection. In this study, the protective effects of the recombinant OmpA protein fragments in E. coli intracerebral infections were investigated. 



 

Methods:

The effects of E. coli intracerebral infection on cytokine and chemokine expression were determined. We also used various recombinant fragments of the OmpA protein to investigate the effects of these recombinant OmpA protein fragments on cytokine and chemokine expression. 



 

Results:

In this study, we demonstrated that the expression of interleukin-17 and other cytokines, chemokines, inducible nitric oxide synthase, and cyclooxygenase-2 are involved in the inflammatory processes of intracerebral E. coli infection. We also demonstrated that specific recombinant OmpA protein fragments (L1–3, L2–3, L2–4, and L3) can regulate cytokine, chemokine, nitric oxide synthase, and cyclooxygenase-2 expression and, subsequently, protect mice from death caused by intracerebral infection of E. coli. 



 

Conclusion:

This finding indicates the potential for developing a new therapeutic approach to improve the prognosis of bacterial meningitis. 



 

Key words:

bacterial meningitis, Escherichia coli, IL-17, NOS-2, outer membrane protein A