Protection against Clostridioides difficile disease by a naturally avirulent strain

Area of Science:

• Microbiology
• Infectious Diseases
• Gastroenterology

Background:

• Clostridioides difficile is a major cause of healthcare-associated infections.
• Gut dysbiosis contributes to C. difficile infection (CDI) and its recurrence.
• Current therapies for recurrent CDI are expensive and do not prevent initial infections.

Purpose of the Study:

• To investigate the protective potential of an avirulent C. difficile strain against virulent strains.
• To elucidate the mechanism underlying the protective effect of the avirulent strain.

Main Methods:

• Coinfection model in mice using an avirulent (ST1-75) and a virulent (R20291) C. difficile strain.
• Metabolic analysis to compare nutrient utilization between strains.
• Amino acid supplementation experiments.

Main Results:

• The avirulent ST1-75 strain protected mice from colitis induced by the virulent R20291 strain when coinfected.
• ST1-75 demonstrated a faster depletion of amino acids compared to R20291.
• Supplementing amino acids abolished the competitive advantage of ST1-75, indicating nutrient depletion as the mechanism.

Conclusions:

• Inter-strain nutrient depletion is a viable mechanism for controlling C. difficile growth.
• The avirulent ST1-75 strain shows potential as a biotherapeutic agent for preventing CDI in high-risk individuals.