Hfq negatively regulates type III secretion in EHEC and several other pathogens
Elizabeth A Shakhnovich1, Brigid M Davis, Matthew K Waldor
1Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA.
Molecular Microbiology
|August 26, 2009
Summary
The Hfq protein negatively regulates the Type III Secretion System (T3SS) in enterohaemorrhagic Escherichia coli (EHEC). Deleting Hfq increases T3SS expression, impacting pathogen virulence.
Area of Science:
- Microbiology
- Molecular Biology
- Bacteriology
Background:
- Hfq (Host Factor 2) is a crucial RNA-binding protein regulating gene expression post-transcriptionally.
- Enterohaemorrhagic Escherichia coli (EHEC) relies on a Type III secretion system (T3SS) for virulence.
- The LEE pathogenicity island encodes the T3SS in EHEC.
Purpose of the Study:
- To investigate the role of Hfq in regulating the T3SS in EHEC.
- To understand how Hfq influences the expression of LEE- and non-LEE-encoded T3 effectors.
Main Methods:
- Gene deletion mutant analysis (hfq deletion).
- Transcriptional analysis of LEE and non-LEE genes.
- Assessment of T3SS complex formation and effector secretion.
- Investigation of the role of Ler (LEE regulator).
Main Results:
- Hfq deletion in EHEC led to significantly elevated transcript levels for all 41 LEE genes and numerous non-LEE-encoded T3 effectors.
- Increased transcripts correlated with enhanced formation of functional T3SS secretion complexes and higher effector secretion.
- The upregulation of LEE transcripts was dependent on Ler, with evidence suggesting direct Hfq-mediated negative regulation of the ler transcript.
- Hfq's role in negatively regulating T3SSs was observed in other pathogens.
Conclusions:
- Hfq acts as a negative regulator of the T3SS in EHEC, coordinating the expression of the secretion apparatus and its effectors.
- Hfq-mediated regulation of T3SSs, potentially involving sRNAs, appears to be a conserved mechanism across different bacterial pathogens to control virulence factor expression.
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