Hypusination in intestinal epithelial cells protects mice from infectious colitis

Area of Science:

• Microbiology
• Cell Biology
• Gastroenterology

Background:

• Enteropathogenic Escherichia coli (EPEC) causes diarrheal disease via attaching/effacing (A/E) lesions.
• Polyamines, like spermidine, are crucial for intestinal homeostasis.
• Dehypusine synthase (DHPS) catalyzes hypusination of eukaryotic translation initiation factor 5A (EIF5A), impacting protein translation.

Purpose of the Study:

• To investigate the role of hypusination in the host response to A/E pathogen infections.
• To elucidate the protective mechanisms of hypusination in the intestinal epithelium.

Main Methods:

• Infection of colonic epithelial cells and colon organoids with EPEC.
• Infection of mice with Citrobacter rodentium (a rodent EPEC model).
• Genetic deletion of Dhps in intestinal epithelial cells of mice.
• Transcriptome analysis and assessment of reactive aldehyde detoxification pathways.

Main Results:

• DHPS and EIF5A hypusination levels increased during EPEC and C. rodentium infections.
• Specific deletion of Dhps in intestinal cells exacerbated C. rodentium-induced colitis.
• Dhps-deficient mice showed impaired detoxification of reactive aldehydes and increased electrophile adducts.

Conclusions:

• Hypusination in intestinal epithelial cells is protective against A/E pathogen-induced infectious colitis.
• DHPS-mediated hypusination supports aldehyde detoxification, mitigating host tissue damage.