Clostridioides difficile binary toxin CDT induces biofilm-like persisting microcolonies

Area of Science:

• Microbiology
• Gastroenterology
• Infectious Diseases

Background:

• Clostridioides difficile infection (CDI) presents with varied symptoms, from diarrhea to colitis.
• High CDI relapse rates pose a significant clinical challenge.
• The binary toxin (CDT) from C. difficile is linked to increased relapse, but its precise role remains unclear.

Purpose of the Study:

• To elucidate the physiological role of CDT in C. difficile pathogenesis.
• To investigate CDT's contribution to C. difficile colonization and persistence in the gut.

Main Methods:

• Utilized hypoxic Transwell and Intestine-on-Chip models simulating intestinal conditions.
• Challenged models with both CDT-producing (CDT+) and non-producing (CDT-) C. difficile strains.
• Observed microcolony formation and vancomycin resistance in infected mouse models.

Main Results:

• CDT induces mucin-associated microcolonies, enhancing C. difficile colonization.
• These microcolonies exhibit biofilm-like properties, increasing vancomycin resistance.
• Similar biofilm-like microcolonies were found in the colons of infected mice.

Conclusions:

• CDT promotes the formation of biofilm-like microcolonies, enhancing C. difficile persistence.
• This mechanism contributes to increased CDI relapse rates.
• Targeting CDT may offer new strategies for CDI management.