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Directed Protein Packaging within Outer Membrane Vesicles from Escherichia coli: Design, Production and Purification
Published on: November 16, 2016
Recombinant OmpA protein fragments mediate interleukin-17 regulation to prevent Escherichia coli meningitis
Wen-Shyang Hsieh1, Yi-Yuan Yang2, Pei-Hsuan Lin3
1Department 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.
Insights
Specific OmpA protein fragments show potential in protecting neonatal mice from bacterial meningitis caused by E. coli. These fragments regulate inflammatory responses, offering a promising new therapeutic avenue for this severe infection.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Neonatal bacterial meningitis is a severe condition with high morbidity, despite decreased mortality.
- Neurological complications affect approximately 40% of survivors.
- Escherichia coli is a common causative agent of neonatal meningitis.
Purpose of the Study:
- To investigate the protective effects of recombinant OmpA protein fragments against E. coli intracerebral infections.
- To determine the impact of these fragments on inflammatory responses.
Main Methods:
- Assessed the effects of E. coli intracerebral infection on cytokine and chemokine expression.
- Utilized recombinant OmpA protein fragments (L1-3, L2-3, L2-4, L3) to evaluate their influence on inflammatory markers.
Main Results:
- Identified interleukin-17 and other cytokines/chemokines, inducible nitric oxide synthase, and cyclooxygenase-2 as key players in E. coli-induced inflammation.
- Demonstrated that specific OmpA fragments regulate these inflammatory mediators.
- Showed that these fragments protect mice from lethal E. coli intracerebral infection.
Conclusions:
- Recombinant OmpA protein fragments exhibit therapeutic potential for bacterial meningitis.
- These findings suggest a novel therapeutic strategy to improve outcomes for bacterial meningitis patients.
Background:
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.
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