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Published on: October 22, 2013
Glucuronic acid confers colonization advantage to enteric pathogens
Thibaut Rosay1,2, Angel G Jimenez2, Vanessa Sperandio1,2
1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706.
Inhibiting microbial β-glucuronidase reactivates glucuronic acid (GlcA) and reduces pathogen colonization in the gut. This suggests β-glucuronidase inhibitors are a promising therapeutic strategy for enteric infections.
Area of Science:
- Microbiology
- Gastroenterology
- Pharmacology
Background:
- Glucuronidation detoxifies compounds, but microbial β-glucuronidases can reactivate them in the gut.
- Enteric pathogens utilize related sugars for colonization, but glucuronic acid's role was unclear.
Purpose of the Study:
- To investigate the role of glucuronic acid (GlcA) in enteric pathogen colonization.
- To evaluate the therapeutic potential of microbial β-glucuronidase inhibitors (GUSi) against gut infections.
Main Methods:
- Administered GUSi to mice infected with *Citrobacter rodentium*.
- Performed metagenomic analysis to assess microbiota changes.
- Assessed pathogen colonization, virulence, and host inflammation.
- Utilized bacterial mutants unable to catabolize GlcA.
- Colonized germfree mice with specific *E. coli* strains.
Main Results:
- GUSi treatment significantly decreased *C. rodentium* colonization without affecting virulence or host inflammation.
- GUSi did not alter the overall intestinal microbiota composition.
- Pathogens utilize GlcA as a carbon source for expansion.
- Mutants deficient in GlcA catabolism showed reduced colonization and were insensitive to GUSi.
- Commensal bacteria lacking β-glucuronidase production reduced pathogen colonization.
Conclusions:
- GlcA provides a colonization advantage to enteric pathogens by serving as a metabolic nutrient.
- Inhibitors of microbial β-glucuronidases represent a novel therapeutic approach for enteric infections.
- This strategy offers a targeted treatment without disrupting host physiology or the gut microbiota.
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