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Uropathogenic Escherichia coli Epigenetically Manipulate Host Cell Death Pathways.
Zhengguo Zhang1, Ming Wang1, Florian Eisel1
1Unit of Reproductive Biology, Department of Anatomy and Cell Biology.
The Journal of Infectious Diseases
|December 2, 2015
Summary
Uropathogenic Escherichia coli (UPEC) prevents host cell death by epigenetically silencing BIM expression. This mechanism blocks apoptosis, contributing to frequent urinary tract infections.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Uropathogenic Escherichia coli (UPEC) causes frequent human urinary tract infections.
- UPEC is known to subvert innate immunity, but its role in host cell death pathways is unclear.
Purpose of the Study:
- To investigate how UPEC interferes with host cell death pathways.
- To elucidate the molecular mechanisms underlying UPEC-induced modulation of apoptosis.
Main Methods:
- Analysis of protein kinase B (Akt/PKB) signaling pathway activation.
- Assessment of mammalian forkhead box O (FOXO) transcription factor activity.
- Investigation of BIM (Bcl-2-like protein 11) expression and its regulation.
- Epigenetic analysis, including histone acetylation at the BIM promoter.
Main Results:
- UPEC abrogates Akt/PKB signaling, leading to FOXO activation.
- UPEC suppresses BIM expression, attenuating caspase 3 activation and blocking apoptosis.
- BIM expression is epigenetically silenced via decreased histone 4 acetylation at the BIM promoter.
Conclusions:
- UPEC employs epigenetic silencing of BIM to prevent apoptosis.
- This mechanism represents a novel strategy used by UPEC to promote infection and survival.
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