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Volume 49, Number 3, June 2016

Recombinant outer membrane protein A fragments protect against Escherichia coli meningitis


Wen-Shyang Hsieh, Yi-Yuan Yang, Hsin-Yi Yang, Yu-Shan Huang, Hsueh-Hsia Wu


Received: July 10, 2014       Accepted: July 31, 2014   

 

Corresponding author:

Corresponding author. Hsueh-Hsia Wu, School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Number 250, Wu-Hsing Street, Taipei 11031, Taiwan. 



 

Background and purpose: 

Although the mortality rates have decreased over the past few decades, neonatal meningitis is still a severe disease with high morbidity. Moreover, approximately 40% of survivors exhibit neurological sequelae. Escherichia coli is the major Gram-negative bacterial pathogen in neonatal meningitis. The N-terminal β-barrel domain of the outer membrane protein A (OmpA) of E. coli is essential for effective protein conformation and function and contains four surface-exposed hydrophilic loops. In this study, we expressed different fragments of the four ring structures of the N-terminal domain, and investigated whether these recombinant OmpA fragments can protect mice from death after E. coli infection. 



 

Methods:

We expressed the recombinant proteins of the following OmpA fragments by using molecular cloning of Loop 1–2, Loop 1–3, Loop 1–4, Loop 2–3, Loop 2–4, and Loop 3–4. Animal experiments were subsequently performed to investigate the effects of these recombinant OmpA fragments on the survival of C57BL/6 mice after intracerebral E. coli RS218 administration. 



 

Results:

This study demonstrated that the recombinant Loop 1–3, Loop 2–3, and Loop 2–4 fragments of OmpA can protect mice from intracerebral E. coli infection. 



 

Conclusion:

In bacterial meningitis, although antibiotic therapy is the first choice for management, neurological complications can seldom be averted. Based on the results of the present study, we intend to establish an effective therapeutic application for E. coli meningitis. 



 

Key words:

bacterial meningitis, Escherichia coli, outer membrane protein A (OmpA)