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Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
The membrane as a target for controlling hypervirulent Clostridium difficile infections
Xiaoqian Wu1, Philip T Cherian, Richard E Lee
1Department of Biology, University of Texas at Arlington, Arlington, TX 76019, USA.
The Journal of Antimicrobial Chemotherapy
|December 25, 2012
Summary
Clostridium difficile infections are hard to treat because stationary-phase cells resist antibiotics. Disrupting the bacterial membrane offers a novel way to kill both growing and non-growing C. difficile cells.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Research
Background:
- Clostridium difficile infections cause significant diarrheal illness.
- The stationary phase of C. difficile is resistant to conventional antibiotic treatments.
- Targeting the bacterial membrane may offer a new strategy against C. difficile.
Purpose of the Study:
- To investigate membrane-disrupting agents as a method to control C. difficile.
- To assess the efficacy of these agents against both growing and non-growing C. difficile cells.
- To explore the impact on toxin production and sporulation.
Main Methods:
- Tested bactericidal activities of membrane-active agents against C. difficile cultures.
- Assessed effects on ATP synthesis, toxin A/B, and sporulation.
- Evaluated agent activity in the presence of rodent caecal contents.
Main Results:
- Most membrane-active agents killed both logarithmic and stationary-phase C. difficile.
- Agents caused rapid viability loss, reduced ATP, toxins, and spores.
- Proton ionophore activity increased as C. difficile growth decreased.
Conclusions:
- C. difficile is highly susceptible to agents targeting its membrane and bioenergetics.
- The clostridial membrane represents a novel antimicrobial target.
- This approach could lead to new treatments for C. difficile infections.
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