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The Clostridium difficile Dlt Pathway Is Controlled by the Extracytoplasmic Function Sigma Factor σV in Response to
Emily C Woods1, Kathryn L Nawrocki1, Jose M Suárez1
1Department of Microbiology and Immunology, Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA.
Infection and Immunity
|April 13, 2016
Summary
Clostridium difficile resistance to lysozyme involves the Dlt pathway, regulated by sigma V (σ(V)). This pathway
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Clostridium difficile is a significant cause of hospital-acquired infections and antibiotic-associated diarrhea.
- Host antimicrobial proteins (AMPs), like lysozyme, normally inhibit bacterial colonization but C. difficile evades them.
- The Dlt pathway enhances C. difficile surface charge, contributing to AMP resistance.
Purpose of the Study:
- To investigate the genetic mechanisms regulating the Dlt pathway in C. difficile.
- To understand how C. difficile survives in the gut despite host defenses.
Main Methods:
- Construction and analysis of dlt and sigV mutants.
- Lysozyme growth assays.
- Reporter gene fusions and 5' RACE to identify promoter elements.
- Virulence assessment in a hamster infection model.
Main Results:
- A dlt null mutant showed impaired growth in lysozyme.
- Lysozyme induced dltDABC operon expression.
- A mutant lacking the ECF sigma factor σ(V) failed to induce dlt expression in response to lysozyme.
- Both sigV and dlt mutants exhibited increased virulence in the hamster model.
Conclusions:
- Lysozyme induces C. difficile cell wall d-alanylation via the Dlt pathway in a σ(V)-dependent manner.
- This regulatory pathway is crucial for C. difficile virulence in vivo.
- Understanding this mechanism offers potential therapeutic targets.
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