title: Gallstones play a significant role in Salmonella spp. gallbladder colonization and carriage.
abstract: Salmonella enterica serovar Typhi can colonize the gallbladder and persist in an asymptomatic carrier state that is frequently associated with the presence of gallstones. We have shown that salmonellae form bile-mediated biofilms on human gallstones and cholesterol-coated surfaces in vitro. Here, we test the hypothesis that biofilms on cholesterol gallbladder stones facilitate typhoid carriage in mice and men. Naturally resistant (Nramp1(+/+)) mice fed a lithogenic diet developed cholesterol gallstones that supported biofilm formation during persistent serovar Typhimurium infection and, as a result, demonstrated enhanced fecal shedding and enhanced colonization of gallbladder tissue and bile. In typhoid endemic Mexico City, 5% of enrolled cholelithiasis patients carried serovar Typhi, and bacterial biofilms could be visualized on gallstones from these carriers whereas significant biofilms were not detected on gallstones from Escherichia coli infected gallbladders. These findings offer direct evidence that gallstone biofilms occur in humans and mice, which facilitate gallbladder colonization and shedding.
authors.affiliation: Department of Molecular Virology, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Crawford
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosales-Reyes
authors.forename: María de la Luz
authors.initials: Mde L
authors.lastname: Ramírez-Aguilar
authors.forename: Oscar
authors.initials: O
authors.lastname: Chapa-Azuela
authors.forename: Celia
authors.initials: C
authors.lastname: Alpuche-Aranda
authors.forename: John S
authors.initials: JS
authors.lastname: Gunn
mesh_terms: D000818:Animals; D018441:Biofilms; D002353:Carrier State; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D042882:Gallstones / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D051379:Mice; D008855:Microscopy, Electron, Scanning; D012486:Salmonella typhimurium / Q000254:growth & development*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D002784:Cholesterol; D000099173:Natural Resistance-associated Macrophage Protein 1