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Self-perpetuating epigenetic pili switches in bacteria
Aaron Hernday1, Margareta Krabbe, Bruce Braaten
1Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara 93117, USA.
Summary
Bacteria use epigenetic phase variation to control pili expression. DNA methylation and regulatory proteins like Lrp and PapI dictate switching between pili ON and OFF states, crucial for bacterial adhesion and infection.
Area of Science:
- Microbiology
- Epigenetics
- Molecular Biology
Background:
- Bacteria utilize epigenetic phase variation for regulating cell surface pili-adhesin complexes.
- The pyelonephritis-associated pili (pap) system involves complex regulation of gene expression states (ON and OFF).
Purpose of the Study:
- To elucidate the epigenetic mechanism controlling phase variation in the pap system.
- To understand the roles of DNA methylation and regulatory proteins (Lrp, PapI, PapB, CAP, Dam) in switching between pili ON and OFF states.
Main Methods:
- Analysis of DNA binding sites for regulatory proteins (Lrp, CAP).
- Investigation of DNA adenine methylase (Dam) methylation targets (GATC sites).
- Characterization of regulatory interactions and their impact on gene transcription.
Main Results:
- Lrp binding sites and Dam methylation patterns differ between phase ON and OFF states.
- Phase OFF involves Lrp at proximal sites, inhibiting methylation and blocking transcription.
- Transition to phase ON requires DNA replication and specific methylation patterns, with Lrp at distal sites activating transcription.
Conclusions:
- Epigenetic control via DNA methylation and protein-DNA interactions governs pili phase variation.
- A coordinated mechanism involving Lrp, PapI, PapB, and Dam ensures stable ON and OFF states.
- This regulation is critical for bacterial adhesion and pathogenesis.