Inflammation may add to the determination of C. diff disease, shows study
- Post By : Kumar Jeetendra
- Source: North Carolina State University
- Date: 19 Jan,2021
A new study from North Carolina State University indicates that the inflammation brought on by Clostridioides difficile (C. diff) infection gives the pathogen a two-fold advantage: by both creating an inhospitable environment for competing bacteria and supplying nutrients that enable C. diff to thrive.
C. diff is a bacterium that causes diarrhea, often with severe or even fatal effects. As part of its development cycle, C. diff produces two toxins that cause inflammation and damage the lining of the gut.
“C. diff thrives when other microbes in the gut are absent – that is the reason why it is more prevalent following antibiotic treatment,” says Casey Theriot, associate professor of infectious disease at NC State and corresponding author of the study.
C. diff’s toxins damage the cells that line the gut. 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.”
Casey Theriot, Associate Professor of Infectious Disease and Study Corresponding Author, North Carolina State University
“However, when colonizing the gut, C. diff also generates two large toxins, TcdA and TcdB, which cause inflammation. We wanted to understand if these inflammation-causing radicals really give C. diff a survival advantage – if the pathogen can exploit an inflamed environment so as to thrive.”
Theriot and former NC State postdoctoral researcher Josh Fletcher led a group that analyzed two varieties of C. diff – one which generated the toxins and a genetically modified strain that did not – both in vitro and in a mouse model. In both versions, toxin-producing C. diff was associated with increased inflammation and cellular damage.
Finally, in vitro experiments revealed that C. diff was able to use amino acids from hydration for expansion.
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 inducing inflammation, C. diff both eliminates competition for resources and creates more resources for its own development.
“I always found it intriguing that C. diff causes such extreme inflammation,” Fletcher says. “Our research indicates that this inflammation may contribute to the persistence of C. diff in the gut environment, prolonging infection.”
Fletcher, J. R., et al. (2021) Clostridioides difficile exploits toxin-mediated inflammation to alter the host nutritional landscape and exclude competitors from the gut microbiota. Nature Communications. doi.org/10.1038/s41467-020-20746-4.