title: Colonization of cecum is important for development of persistent infection by Yersinia pseudotuberculosis.
abstract: Yersiniosis is a human disease caused by the bacterium Yersinia pseudotuberculosis or Yersinia enterocolitica. The infection is usually resolved but can lead to postinfectious sequelae, including reactive arthritis and erythema nodosum. The commonly used Yersinia mouse infection model mimics acute infection in humans to some extent but leads to systemic infection and eventual death. Here, we analyzed sublethal infection doses of Y. pseudotuberculosis in mice in real time using bioluminescent imaging and found that infections using these lower doses result in extended periods of asymptomatic infections in a fraction of mice. In a search for the site for bacterial persistence, we found that the cecum was the primary colonization site and was the site where the organism resided during a 115-day infection period. Persistent infection was accompanied by sustained fecal shedding of cultivable bacteria. Cecal patches were identified as the primary site for cecal colonization during persistence. Y. pseudotuberculosis bacteria were present in inflammatory lesions, in localized foci, or as single cells and also in neutrophil exudates in the cecal lumen. The chronically colonized cecum may serve as a reservoir for dissemination of infection to extraintestinal sites, and a chronic inflammatory state may trigger the onset of postinfectious sequelae. This novel mouse model for bacterial persistence in cecum has potential as an investigative tool to unveil a deeper understanding of bacterial adaptation and host immune defense mechanisms during persistent infection.
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden anna.fahlgren@molbiol.umu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Fahlgren
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
authors.forename: Kemal
authors.initials: K
authors.lastname: Avican
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Westermark
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.
authors.forename: Roland
authors.initials: R
authors.lastname: Nordfelth
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Fällman
mesh_terms: D000818:Animals; D057138:Bacterial Shedding; D002432:Cecum / Q000382:microbiology*; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005260:Female; D008163:Luminescent Measurements; D051379:Mice; D051598:Whole Body Imaging; D015011:Yersinia pseudotuberculosis / Q000502:physiology*; D015012:Yersinia pseudotuberculosis Infections / Q000382:microbiology*