title: Postnatal development of the small intestinal mucosa drives age-dependent, regio-selective susceptibility to Escherichia coli K1 infection.
abstract: The strong age dependency of neonatal systemic infection with Escherichia coli K1 can be replicated in the neonatal rat. Gastrointestinal (GI) colonization of two-day-old (P2) rats leads to invasion of the blood within 48 h of initiation of colonization; pups become progressively less susceptible to infection over the P2-P9 period. We show that, in animals colonized at P2 but not at P9, E. coli K1 bacteria gain access to the enterocyte surface in the mid-region of the small intestine and translocate through the epithelial cell monolayer by an intracellular pathway to the submucosa. In this region of the GI tract, the protective mucus barrier is poorly developed but matures to full thickness over P2-P9, coincident with the development of resistance to invasion. At P9, E. coli K1 bacteria are physically separated from villi by the mucus layer and their numbers controlled by mucus-embedded antimicrobial peptides, preventing invasion of host tissues.
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, SE-405 30, Gothenburg, Sweden.
authors.forename: George M H
authors.initials: GM
authors.lastname: Birchenough
authors.affiliation: School of Pharmacy, University College London, London, WC1N 1AX, UK.
authors.forename: Fatma
authors.initials: F
authors.lastname: Dalgakiran
authors.affiliation: School of Pharmacy, University College London, London, WC1N 1AX, UK.
authors.forename: Luci A
authors.initials: LA
authors.lastname: Witcomb
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, SE-405 30, Gothenburg, Sweden.
authors.forename: Malin E V
authors.identifier: 0000-0002-4237-6677
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: School of Pharmacy, University College London, London, WC1N 1AX, UK.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: McCarthy
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, SE-405 30, Gothenburg, Sweden.
authors.forename: Gunnar C
authors.identifier: 0000-0002-1900-1869
authors.initials: GC
authors.lastname: Hansson
authors.affiliation: School of Pharmacy, University College London, London, WC1N 1AX, UK. peter.taylor@ucl.ac.uk.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001769:Blood / Q000382:microbiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000254:growth & development* / Q000382:microbiology; D007421:Intestine, Small / Q000166:cytology* / Q000254:growth & development / Q000382:microbiology; D009928:Organ Specificity; D019879:Paneth Cells / Q000166:cytology / Q000382:microbiology; D051381:Rats