Tag Archives: North Carolina State University

Clostridioides diffiicle Thrives In an Inflammed Environement ….Research Study From North Carolina State University

Clostridioides difficile thrives in an inflamed environment by generating toxins that support prolonged infection, according to a study from North Carolina State University.

The study, published in Nature Communications, showed how C. diff produces toxins that cause inflammation, eliminating competing bacteria and releasing peptides and amino acids that support the growth of C. diff.

C. diff thrives when other microbes in the gut are absent – which is why it is more prevalent following antibiotic therapy,” corresponding author Casey Theriot, Ph.D., associate professor of infectious disease at North Carolina State University, said. “But when colonizing the gut,
C. diff. also produces two large toxins, TcdA and TcdB, which cause inflammation. We wanted to know if these inflammation-causing toxins actually give C. diff a survival benefit – whether the pathogen can exploit an inflamed environment in order to thrive.”

Investigators examined two variants of C. diff in vitro and in an antibiotic-treated mouse model. The variants included a wild type C. diff that produces toxins and a genetically modified variant that does not. They found that the wild type C. diff, associated with toxin production, generated more inflammation and tissue damage than the mutant.

To read the article in its entirety, please click on the following link to be redirected:

https://www.contagionlive.com/view/clostridioides-difficile-thrives-in-inflamed-environment

Investigators also found changes in the expression of metabolic genes, with C. diff in the inflamed environment expressing more genes related to carbohydrate and amino acid metabolism that sustains growth.

C. diff’s toxins damage the cells that line the gut,” Theriot said. “These cells contain collagen, which is made up of amino acids and peptides. When collagen is degraded by toxins,
C. diff responds by turning on expression of genes that can use these amino acids for growth.”

Inflammation provided a second benefit to C. diff by creating an inhospitable environment for other bacteria that compete for nutrients. Bacteroidaceae were present in control groups that weren’t infected with toxin-producing C. diff, which was consistent with previous studies that found negative associations between C. diff and Bacteroidaceae.

“I always found it interesting that C. diff causes such intense inflammation,” first author Josh Fletcher, Ph.D., a former postdoctoral researcher at North Carolina State University, said. “Our research shows that this inflammation may contribute to the persistence of C. diff in the gut environment, prolonging infection.”

C. diff is the most significant cause of hospital-acquired diarrhea, causing more than 223,900 infections and 12,800 deaths in the US in 2017, according to a recent report.

The disease has two phases, a spore phase, and vegetative phase. Toxins are released during the vegetative phase, causing diarrhea and other symptoms. But the pathogen is often transmitted during the spore phase, during which it is hardy and isn’t susceptible to gastric acids and alcohol-based hand sanitizer, experts explained during a recent discussion of the disease.

Risks for infection include exposure to C. diff spores and antibiotic use. An investigational drug to prevent the disruption of the gut microbiota by antibiotics is among the most recent developments in the fight against a C diff. infection.

 

Researchers From North Carolina State University Find That Antibiotics Give C.diff. Nutrient-Rich Environment

Using a mouse model, researchers from North Carolina State University have found that antibiotic use creates a “banquet” for Clostridium difficile (C. diff), by altering the native gut bacteria that would normally compete with C. diff for nutrients. The findings could lead to the development of probiotics and other strategies for preventing C. diff infection.

C. diff is a harmful bacterium that can cause severe, recurrent and sometimes fatal infections in the gut. Although the bacteria are commonly found throughout our environment, C. diff infections primarily occur in patients who are taking, or who have recently finished taking, antibiotics.

“We know that antibiotics are major risk factors for C. diff infection because they alter the gut microbiota, or composition of bacteria in the gut, by eliminating the bacteria that are normally there,” says Casey Theriot, assistant professor of infectious disease at NC State and corresponding author of a paper describing the research. “Our latest work suggests that the microbiota may provide natural resistance to C. diff colonization by competing with C. diff for nutrients in that environment; specifically, for an amino acid called proline.”

Theriot and postdoctoral fellow Joshua Fletcher introduced C. diff to antibiotic-treated mice and monitored their gut environment at four intervals: 0, 12, 24, and 30 hours after introduction. They conducted metabolomic and RNA sequencing analysis of the gut contents and the C. diff at these time points to find out which nutrients the bacteria were “eating.” Metabolomics allowed the team to trace the abundance of the nutrients in the gut, and RNA analysis indicated which genes in the C. diff were active in metabolizing nutrients.

The researchers found that the amount of proline in the gut decreased as the population of C. diff increased. Additionally, the amount of a proline byproduct called 5-aminovalerate also increased, indicating that C. diff was metabolizing the proline. The RNA analysis further confirmed C. diff‘s use of proline, as genes related to proline metabolism in C. diff increased during the early stages of colonization, when proline was abundant.

“We’ve been able to show that in the absence of competition C. diff is metabolizing proline and other amino acids in the mouse model, using it as fuel to survive and thrive,” Theriot says. “Hopefully this information could lead to the development of better probiotics, or ‘good’ bacteria that can outcompete C. diff for nutrients in the gut. The ultimate goal is to control these bacteria in ways that don’t rely solely on antibiotics.”

To review article in its entirety please click on the following link to be redirected:

https://www.sciencedaily.com/releases/2018/03/180328204122.htm