Bacteria may be single-celled organisms, but many of them live in communities called biofilms. These thick and often slimy layers of microbes generate a community that is stronger than an individual; biofilms are tough to destroy, can often resist antimicrobials, and enable microbes to thrive. Salmonella bacteria can form a biofilm that produces a fibrous protein called curli amyloid, which can lead to diarrhea during an gut infection. Researchers have now found that this protein is linked to other illnesses as well. The findings have been reported in the journal PLOS Pathogens.
Reactive arthritis (ReA) is a painful inflammatory disease, and impacts around five percent of people that have had a gastrointestinal illness caused by a bacterial infection. Not much is known about what causes ReA, and there are no treatments.
In this work, scientists utilized a mouse model of foodborne diarrhea caused by a Salmonella enterica Typhimurium infection. Clusters of bacteria were seen within weeks of the bacterial infection, and the microbes started making curli. The curli protein caused the immune system to react; antibodies attacking the 'self' were observed. These autoantibodies were against complexes of curli and DNA and were attributed to a system-wide Salmonella infection.
Joint inflammation started in the mice after curli-induced antibody production. Chronic inflammation in the fluid around affected joints and the breakdown of bones, features of ReA, were seen. It seems that when pathogenic bacteria get out of the intestinal tract they can cause serious problems.
"We found specifically that if curli stays in the intestines, its negative inflammatory effects are limited," explained the senior study author Cagla Tukel, Ph.D., Associate Professor in the Department of Microbiology and Immunology at Lewis Katz School of Medicine at Temple University (LKSOM). "But in susceptible individuals, if curli escapes the intestinal tract and enters the circulation, an autoimmune reaction ensues."
"Our findings indicate that curli is a major component of Salmonella that drives autoimmune reactions," Tukel said. "In mice, these reactions were triggered within six weeks of infection, demonstrating that the expression of a bacterial component in the intestine can lead to subsequent autoimmune responses."
A genetic variant has been linked to the production of a protein called HLAB27 and it's a known risk factor for ReA. "The presence of pathogenic curli in the microbiota may precipitate or exacerbate autoimmunity in individuals with HLAB27," Tukel noted.
Tukel's team is planning to confirm these findings in people, and to investigate whether other pathogenic microbes can trigger similar autoimmune responses. They are also studying the link between bacterial curli protein and brain diseases like Alzheimer's.
"Recent research in Parkinson's disease mouse models suggests that curli amyloid fuels neurodegeneration," Tukel said. "The ability of enteric bacterial curli to escape the intestine and reach the systemic circulation raises questions about a potential role in neurodegenerative processes."