Bacterial Curli Fibers Reverse Symptoms of Inflammatory Bowel Disease in Mouse Model

A novel treatment for inflammatory bowel disease based on oral administration of a single dose of purified curli fibers was successfully tested in a mouse model of acute colitis.

Curli are the major protein components of a complex extra-cellular matrix produced by many Enterobacteriaceae. Curli fibers, which share many distinguishing biochemical and structural properties with eukaryotic amyloid fibers, are involved in adhesion to surfaces, cell aggregation, and biofilm formation. Curli also mediate host cell adhesion and invasion, and they are potent inducers of the host inflammatory response.

The structure and biogenesis of curli are unique among bacterial fibers that have been described to date. Structurally and biochemically, curli fibers belong to a growing class of fibrous proteins known as amyloids. Amyloid fiber formation is responsible for several human diseases including Alzheimer's, Huntington's, and prion diseases, although the process of in vivo amyloid formation is not well understood.

Recognition of curli fibers by the Toll-like receptor (TLR)2/1 complex was found to reinforce the membranes lining the bowel, which might counter damage induced by inflammatory bowel disease. To evaluate the therapeutic potential of curli fibers, investigators at Temple University (Philadelphia, PA, USA) studied the effect of purified curli fibers on inflammation in a mouse model of acute colitis.

In the study bone marrow–derived macrophages as well as lamina propria cells were treated with curli fibers of both pathogenic Salmonella enterica serovar Typhimurium and commensal Escherichia coli Nissle 1917 biofilms. In an in vivo experiment, mice were given 0.1 or 0.4 milligrams of purified curli orally one day post administration of 1% 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. Histopathological analysis was performed on distal colonic tissue taken six days post TNBS enema. RNA extracted from colonic tissue was subjected to RT (real time)-PCR.

Results published in the October 14, 2015, online edition of the journal Biofilms and Microbiomes revealed that curli fibers of both pathogenic and commensal bacteria were recognized by TLR2 leading to the production of IL-10 (interleukin-10), an immunomodulatory cytokine of intestinal homeostasis. Treatment of mice with a single dose of curli increased transcript levels of IL-10 in the colon and ameliorated the disease pathology in TNBS-induced colitis. Curli treatment was comparable to the treatment with anti-tumor necrosis factor alpha (anti-TNFalpha) antibodies, a treatment known to reduce the severity of acute colitis in humans and mice.

"The really remarkable finding is that one dose of curli—not a daily dose, but just a single oral dose—decreased inflammation and disease pathology and altered the cytokine profile," said senior author Dr. Çagla Tükel, assistant professor of microbiology and immunology at Temple University.

Related Links:
Temple University