Inflamed environment is C. diff paradise

C. diffis a bacterium that causes diarrhea, often with severe or even fatal consequences. As part of its growth cycle,C. diffproduces two toxins which cause inflammation and damage the lining of the gut.

"C. diffthrives when other microbes in the gut are absent -- which is why it is more prevalent following antibiotic therapy," says Casey Theriot, associate professor of infectious disease at NC State and corresponding author of the research. "But when colonizing the gut,C. diffalso produces two large toxins, TcdA and TcdB, which cause inflammation. We wanted to know if these inflammation-causing toxins actually giveC. diffa survival benefit -- whether the pathogen can exploit an inflamed environment in order to thrive."

Theriot and former NC State postdoctoral researcher Josh Fletcher led a team that studied two varieties ofC. diff-- one that produced the toxins and a genetically modified strain that did not -- both in vitro and in a mouse model. In both models, toxin-producingC. diffwas associated with increased inflammation and cellular damage. Genetic analysis found thatC. diffin an inflamed environment expressed more genes related to carbohydrate and amino acid metabolism. Finally, in vitro experiments demonstrated thatC. diffwas able to utilize amino acids from collagen for growth.

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

The researchers also noted that an inflamed environment suppressed the numbers of other microbes in the gut. So the toxins play a dual role: by causing inflammation,C. diffboth removes competition for resources and creates more resources for its own growth.

"I always found it interesting thatC. diffcauses such intense inflammation," Fletcher says. "Our research shows that this inflammation may contribute to the persistence ofC. diffin the gut environment, prolonging infection."