Developing new drugs

Campylobacter bacteria is the number one cause of bacterial diarrheal illness in the United States, according to the Centers for Disease Control and Prevention. Approximately 1.3 million people are affected each year. In most cases, people become sick from eating raw or undercooked poultry, drinking contaminated water, or consuming unpasteurized milk. Campylobacter jejuni is the species responsible for most human illness, and has been the focus of Dr. Linda Mansfield’s research for many years.

 “By studying enteric pathogens that cause GI disease, we can look at the genes that cause virulence and how they evolve in the host,” Mansfield explains. “This can give us a better understanding of how these bacteria can trigger acute and chronic diseases.”   Mansfield, a University Distinguished Professor who also is an Albert C. and Lois E. Dehn Chair, developed a diagnostic test for C. jejuni and used it to demonstrate how the bacterium can lead to autoimmune diseases, such as inflammatory bowel disease and Guillain-Barré Syndrome, which causes pain, peripheral neuropathy, respiratory paralysis, and sometimes death. While Guillain-Barré Syndrome has only a 5 to 10 percent mortality rate, the time it takes a patient to recover varies widely. Patients also may have permanent nerve damage.

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“By studying enteric pathogens that cause GI disease, we can look at the genes that cause virulence and how they evolve in the host. This can give us a better understanding of how these bacteria can trigger acute and chronic diseases.”

Mansfield’s goal is to find options for future drug development, both therapeutic and preventive. She’s using a mouse model to locate a biomarker in C. jejuni patients that may help scientists predict whether a person will develop Guillain-Barré Syndrome. Her team used high-throughput sequencing and two mouse models—one with conventional mouse microbiota and another with stable human gut microbiota—to see if the structure of the gut microbial community alters the hosts’ GI inflammation or autoimmune response after a C. jejuni infection leads to colitis or Guillain-Barré Syndrome.

 “The data we collected showed that human gut microbiota alters the host-pathogen interactions in the model,” Mansfield says. “In these mice, there were increased colonization of Campylobacter and increased autoantibodies and autoimmune responses, meaning that microbiota composition is another factor that affects susceptibility to Guillain-Barré Syndrome.”