Abstract
Reactive arthritis, an autoimmune disorder, occurs following gastrointestinal infection with invasive enteric pathogens, such as Salmonella enterica. Curli, an extracellular, bacterial amyloid with cross beta-sheet structure can trigger inflammatory responses by stimulating pattern recognition receptors. Here we show that S. Typhimurium produces curli amyloids in the cecum and colon of mice after natural oral infection, in both acute and chronic infection models. Production of curli was associated with an increase in anti-dsDNA autoantibodies and joint inflammation in infected mice. The negative impacts on the host appeared to be dependent on invasive systemic exposure of curli to immune cells. We hypothesize that in vivo synthesis of curli contributes to known complications of enteric infections and suggest that cross-seeding interactions can occur between pathogen-produced amyloids and amyloidogenic proteins of the host.
Highlights
Salmonella enterica serovar (S.) Typhimurium is a common non-typhoidal Salmonella species (NTS), which causes gastroenteritis in immunocompetent individuals [1]
Our manuscript focuses on curli, a ‘functional amyloid’ produced by Salmonella as well as other enteric bacteria
We present the first biochemical evidence that these fibers are produced in the gastrointestinal tract of mice after oral infection, the natural route for Salmonella infections
Summary
Salmonella enterica serovar (S.) Typhimurium is a common non-typhoidal Salmonella species (NTS), which causes gastroenteritis (diarrhea) in immunocompetent individuals [1]. Typhimurium forms multicellular communities called biofilms; these structures involve a thick extracellular matrix composed of curli, cellulose, BapA, and extracellular DNA (eDNA) that has been shown to protect bacteria from various environmental insults including chemicals, osmotic stress, and oxidative stress [7]. The ability of NTS to form biofilms is predicted to be a conserved strategy for increased persistence and survival in non-host environments, which would increase the likelihood of transmission to a new host [8, 9]. Previous work proposed that biofilm formation and aggregation could provide Salmonella with a mechanism to survive the harsh conditions of the host intestinal tract [10,11,12]. Whether Salmonella forms biofilms or biofilm-like aggregates within the human host is not known
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