title: In vivo murine and in vitro M-like cell models of gastrointestinal anthrax.
abstract: Bacillus anthracis is the causative agent of anthrax and is acquired by three routes of infection: inhalational, gastrointestinal and cutaneous. Gastrointestinal (GI) anthrax is rare, but can rapidly result in severe, systemic disease that is fatal in 25%-60% of cases. Disease mechanisms of GI anthrax remain unclear due to limited numbers of clinical cases and the lack of experimental animal models. Here, we developed an in vivo murine model of GI anthrax where spore survival was maximized through the neutralization of stomach acid followed by an intragastric administration of a thiabendazole paste spore formulation. Infected mice showed a dose-dependent mortality rate and pathological features closely mimicking human GI anthrax. Since Peyer's patches in the murine intestine are the primary sites of B. anthracis growth, we developed a human M (microfold)-like-cell model using a Caco-2/Raji B-cell co-culturing system to study invasive mechanisms of GI anthrax across the intestinal epithelium. Translocation of B. anthracis spores was higher in M-like cells than Caco-2 monolayers, suggesting that M-like cells may serve as an initial entry site for spores. Here, we developed an in vivo murine model of GI anthrax and an in vitro M-like cell model that could be used to further our knowledge of GI anthrax pathogenesis.
authors.affiliation: National Center for Biodefense and Infectious Diseases, George Mason University, 10650 Pyramid Place, Manassas, VA 20110, USA. jessica.chertow@nih.gov
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Tonry
authors.forename: Serguei G
authors.initials: SG
authors.lastname: Popov
authors.forename: Aarthi
authors.initials: A
authors.lastname: Narayanan
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
authors.forename: Ramin M
authors.initials: RM
authors.lastname: Hakami
authors.forename: Calvin
authors.initials: C
authors.lastname: Carpenter
authors.forename: Charles
authors.initials: C
authors.lastname: Bailey
authors.forename: Myung-Chul
authors.initials: MC
authors.lastname: Chung
mesh_terms: D000818:Animals; D000881:Anthrax / Q000382:microbiology* / Q000473:pathology; D001408:Bacillus anthracis / Q000472:pathogenicity / Q000502:physiology*; D001422:Bacterial Adhesion / Q000502:physiology; D058491:Bacterial Load; D018988:Bacterial Translocation; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D005260:Female; D005767:Gastrointestinal Diseases / Q000382:microbiology* / Q000473:pathology; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D053208:Kaplan-Meier Estimate; D051379:Mice; D008811:Mice, Inbred DBA; D013171:Spores, Bacterial