title: Recombinant outer membrane protein A fragments protect against Escherichia coli meningitis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Laboratory Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wen-Shyang
authors.initials: WS
authors.lastname: Hsieh
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Yang
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Yang
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Huang
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan; Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address: wuhh@tmu.edu.tw.
authors.forename: Hsueh-Hsia
authors.initials: HH
authors.lastname: Wu
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D006801:Humans; D020814:Meningitis, Escherichia coli / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000276:immunology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D011994:Recombinant Proteins; C078167:OMPA outer membrane proteins
keywords: Escherichia coli; bacterial meningitis; outer membrane protein A (OmpA)