Researchers have discovered a new compound to help prevent Clostridioides difficile (C. diff) infection.

Clostridioides Difficile Infection Prevention

About 500,000 people in the United States suffer from gastrointestinal infections from Clostridioides difficile (C. diff). Over 20,000 die from the infections.

A compound that could prevent C. diff infection was discovered in a recent mouse study. Diverse bacterial strains cause the infection; some can lead to serious illness, EurekAlert! reported.

Scientists are studying the compound to create novel medication candidates that may one day prevent C. diff infections.

Life-threatening diarrhea brought on by C. diff infection is typically a medication side effect. Only two main medications - both are antibiotics- are allowed to treat it after the infection.

According to Jacqueline Phan, a doctorate student in chemistry working in the lab of Ernesto Abel-Santos, a biochemistry professor at the University of Nevada, Las Vegas, C. diff infection is a significant financial burden on the US healthcare system, costing $3 to $4 billion annually. Instead of treating patients solely when they show symptoms of the virus, the new research aims to develop a prophylactic medicine that might be used to treat susceptible people before the infection develops.

Several of the novel chemicals they have created with just one treatment can protect mice for multiple days. Also, they discovered that these substances seem to circulate in a loop between the liver and the gut, indicating that the liver is permitting a gradual release of these substances to the gut.

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Why C. Diff Is Successful At Infection?

One explanation for C. diff's effectiveness in spreading infection is its capacity to produce dormant spores that can last on surfaces or in the gastrointestinal tract. The spores won't begin to germinate and develop into the cells that lead to symptomatic infection until they reach the nutrient-rich intestinal lumen.

Another well-known spore-forming kind of bacteria is anthrax, according to Abel-Santos. She began pondering how the spores, which are just sand particles, detect their environment and begin the germination process that transforms them into regular living organisms after the anthrax assaults in 2001. Abel-Santos understood that preventing infectious diseases like C.diff might be accomplished by focusing on the germination process.

To discover a strategy to stop C.diff, the researchers took advantage of the ability of a spore to change its optical characteristics as it begins to germinate. By measuring the optical density of the spores after incubation with one of the chemicals, they could test hundreds of different substances.

In a mouse model of C. diff, compounds that prevented spore germination at extremely low doses in the micromolar range were further examined. The best contender was the bile salt analog CaPA, which has an aniline substitution.

Moreover, the researchers observed variations in C. diff infection severity related to food and sex. They also found that infection severity in female mice was associated with the estrous cycle the day before.

Based on the findings, scientists are investigating how nutrition can impact the gut microbiota and, consequently, C. diff infection. They also examine how the mouse estrous cycle may influence the results.

Phan will present the new research at Discover BMB, the American Society for Biochemistry and Molecular Biology annual meeting from March 25 to 28 in Seattle. 

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