EMBARGOED UNTIL: Tuesday 5/21, 3 PM MDT
(Symposium Session 219)
UNC Chapel Hill
Chapel Hill, NC, United States
Phone: (919) 843-2863
Every year, the intestinal pathogen Clostridium difficile (commonly referred to as ‘C. diff’) sends over 300,000 Americans to the hospital with an estimated annual treatment cost approaching $5 billion. Antibiotic treatment for other conditions is the primary risk factor for C. diff infection, as a healthy community of beneficial gut bacteria appears to be the best defense against this pathogen. The symptoms of C. diff infection range from bloody diarrhea to fatal colitis, and 20-35% of patients will suffer at least one recurrence after their treatment is complete. The bacterium is resistant to multiple antibiotics, and is so difficult to eradicate that patients are turning to ‘fecal transplants’ to suppress their infections by repopulating their digestive systems with beneficial bacteria. The resilience and persistence of this organism within the harsh conditions of the human digestive system are very poorly understood. Erin B. Purcell and Rita Tamayo have discovered that nutrient availability in C. diff’s environment—the lab media or the human large intestine—influence the bacterium’s ability to survive and reproduce in stressful conditions. As the nutrient conditions within the large intestine can potentially be modulated by dietary changes, this work is the first step towards treatments that will make the human gut a stressful environment in which C. diff cannot survive.
Dr. Purcell and Dr. Tamayo performed this research at the University of North Carolina, Chapel Hill, in the Department of Microbiology and Immunology. Funding was provided by the National Institutes of Diabetes and Digestive and Kidney Diseases, of the U.S. National Institutes of Health. Dr. Purcell presented this work on May 21, 2013, at the 2013 General Meeting of the American Society for Microbiology in Denver, CO.
C. diff is a flagellated, motile bacterium that causes disease when it produces toxins which damage the epithelial lining of the intestine. C. diff motility, attachment to surfaces, and toxin production only occur in certain conditions but the signals that trigger these processes are mostly unknown. Drs. Purcell and Tamayo had previously shown that an intracellular signaling molecule called c-di-GMP that regulates complex processes in other bacteria controls motility and aggregation in C. diff. To determine how C. diff responds to low levels of c-di-GMP, they artificially raised the expression level of a C. diff gene that encodes an enzyme—PdcA—that degrades c-di-GMP. This had a measurable effect on C. diff motility in nutrient-rich media, but not in nutrient-poor media, indicating that nutrient availability in the environment regulates levels of c-di-GMP in the bacterium. Further work revealed that elevated PdcA and diminished c-di-GMP allowed C. diff to continue dividing during complete nutrient starvation, when the cells normally halt reproduction to conserve energy. This means that c-di-GMP also regulates the strategies C. diff employs to survive adverse conditions such as starvation. This work identifies a C. diff pathway controlling the organism’s response to stressful conditions, building towards new strategies to combat the bacterium behind a growing crisis in public health.