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06:51
Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
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C. difficile exploits a host metabolite produced during toxin-mediated disease
Kali M Pruss1, Justin L Sonnenburg2
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|April 29, 2021
Summary
Clostridium difficile utilizes host-derived sorbitol, produced by aldose reductase during inflammation, to gain a metabolic advantage. This nutrient source is generated in response to the pathogen's own toxin-induced disease.
Area of Science:
- Microbiology
- Pathogen Metabolism
- Host-Pathogen Interactions
Background:
- Enteric pathogens exploit host inflammation for metabolic gain.
- Clostridium difficile causes toxin-mediated colitis, but its metabolic adaptation to inflammation is poorly understood.
Purpose of the Study:
- To elucidate the metabolic strategies of Clostridium difficile during host-induced inflammation.
- To identify nutrient sources utilized by C. difficile in an inflammatory environment.
Main Methods:
- RNA sequencing of wild-type and toxin-deficient C. difficile in a mouse model.
- Integration of bacterial and host genetics to study host-pathogen metabolism.
Main Results:
- C. difficile utilizes dietary and host-derived sorbitol.
- Host sorbitol is produced by aldose reductase, an enzyme upregulated in immune cells during inflammation.
- Aldose reductase activity increases during C. difficile toxin-mediated disease.
Conclusions:
- C. difficile leverages host-derived sorbitol, produced by aldose reductase, as a nutrient during its own induced colitis.
- This highlights a novel mechanism of pathogen adaptation involving host enzyme induction during infection.
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