ZupT Facilitates Clostridioides difficile Resistance to Host-Mediated Nutritional Immunity

Area of Science:

• Microbiology and Immunology
• Pathogen-Host Interactions

Background:

• Clostridioides difficile infection (CDI) is a significant public health concern, characterized by severe colitis and hyperinflammation.
• Host immune responses involve neutrophil infiltration and antimicrobial deployment, including calprotectin, a metal-chelating protein crucial in combating C. difficile.

Purpose of the Study:

• To investigate the mechanisms by which C. difficile survives in the presence of high calprotectin levels during infection.
• To determine the role of the putative zinc transporter, ZupT, in C. difficile's resistance to host nutritional immunity.

Main Methods:

• Assessed ZupT expression in C. difficile under calprotectin-induced conditions.
• Evaluated the growth inhibition of C. difficile wild-type and zupT mutant strains in the presence of calprotectin.
• Utilized a murine model of infection to compare the colonization and persistence of wild-type and zupT mutant C. difficile.

Main Results:

• ZupT is highly expressed by C. difficile when exposed to calprotectin.
• ZupT is essential for protecting C. difficile against calprotectin-mediated growth inhibition.
• zupT mutants exhibit impaired colonization and persistence in a murine model of CDI compared to wild-type strains.

Conclusions:

• Clostridioides difficile employs the ZupT zinc transporter to overcome host nutritional immunity mediated by calprotectin.
• Targeting ZupT or other nutrient acquisition systems in C. difficile represents a potential therapeutic strategy for CDI.