Abstract
Objectives
Involvement of the outer membrane protein C (OmpC) of Escherichia coli in neurodegeneration was investigated using a mouse model.
Results
OmpC formed protease-resistant fibres that exhibited the diagnostic features of an amyloid. The spectral shift in the Congo Red and the thioflavin T assays produced features similar to neurotoxic peptides. Intramuscular administration of OmpC in mice resulted in spongiform neurodegeneration of the brain through calcium-dependent apoptosis and also showed upregulation of apoptosis related genes. Immunolocalization of OmpC in brain demonstrated the direct involvement of the porin in neurodegeneration and formation of spongiform encephalopathy.
Conclusion
We have demonstrated the ability of OmpC of E. coli to induce neurodegeneration in mice.
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Acknowledgments
We thank the Directors of CIBA and ERI, for providing necessary facilities to carry out the experiments. We thank Dr. S Antony Ceasar, N. Kalaimani, S. V. Alavandi and M. Poornima for critical evaluation of the manuscript. Dr. V. Sankar, Dr. S. Skylab and Dr. Krubakaran for their histopathological analysis and D. L. Mohanlal for technical assistance. We are grateful to Prof. John Cullum for correcting the manuscript. We are indebted to Dr Shankar, NIMHANS, Bangalore for providing human brain tissues. We thank ERI for financial support.
Conflict of interest
The authors declare that there are no conflicts of interest.
Supporting information
Supplementary Table 1 Details of primers used for the qRT-PCR analysis.
Supplementary Fig. 1 Neuropathology of porin treated mice hippocampus and cerebellum.
Supplementary Fig. 2 Porin trafficking in the experimental mice.
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Joseph Sahaya Rajan, J., Chinnappan Santiago, T., Singaravel, R. et al. Outer membrane protein C (OmpC) of Escherichia coli induces neurodegeneration in mice by acting as an amyloid. Biotechnol Lett 38, 689–700 (2016). https://doi.org/10.1007/s10529-015-2025-8
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DOI: https://doi.org/10.1007/s10529-015-2025-8