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Conserved oligopeptide permeases modulate sporulation initiation in Clostridium difficile
Adrianne N Edwards1, Kathryn L Nawrocki1, Shonna M McBride2
1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
Infection and Immunity
|July 30, 2014
Summary
Inactivating oligopeptide permeases (Opp and App) in Clostridium difficile accelerates sporulation and increases virulence. This contrasts with Bacillus species, suggesting Opp and App indirectly inhibit C. difficile sporulation and pathogenesis.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Clostridium difficile forms dormant spores for survival and transmission.
- Sporulation regulation in C. difficile differs from other spore-forming bacteria.
- Oligopeptide permeases (Opp and App) typically promote sporulation in Bacillus species.
Purpose of the Study:
- Investigate the role of Opp and App in C. difficile sporulation.
- Determine if Opp and App regulate sporulation and virulence in C. difficile.
- Understand the conserved vs. divergent functions of Opp and App.
Main Methods:
- Genetic inactivation of opp and app genes in C. difficile.
- Analysis of early sporulation gene expression.
- In vitro sporulation assays.
- Assessment of virulence and spore recovery in a hamster infection model.
Main Results:
- Opp and App inactivation led to earlier sporulation gene expression and increased in vitro sporulation.
- Disruption of opp and app enhanced C. difficile virulence in hamsters.
- Increased spore loads were recovered from feces of infected hamsters lacking Opp and App.
- Opp and App likely inhibit sporulation indirectly via SinR/SinI regulation.
Conclusions:
- Opp and App transporters have an inhibitory role in C. difficile sporulation and virulence, contrasting with Bacillus species.
- Nutrient availability likely influences C. difficile sporulation and pathogenesis in vivo.
- Opp and App represent potential targets for controlling C. difficile infections.
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