Postnatal development of the small intestinal mucosa drives age-dependent, regio-selective susceptibility to Escherichia coli K1 infection

• Published in: Scientific reports 2017-03, Vol.7 (1), p.83-83, Article 83
• Main Authors: Birchenough, George M. H., Dalgakiran, Fatma, Witcomb, Luci A., Johansson, Malin E. V., McCarthy, Alex J., Hansson, Gunnar C., Taylor, Peter W.
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 14/19; 14/28; 14/32; 14/34; 631/326/421; 692/420/254; Animals; Animals, Newborn; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Blood - microbiology; Cells, Cultured; colonization; Disease Models, Animal; Escherichia coli - physiology; Escherichia coli Infections - microbiology; gene-expression; Humanities and Social Sciences; Intestinal Mucosa - growth & development; Intestinal Mucosa - microbiology; Intestine, Small - cytology; Intestine, Small - growth & development; Intestine, Small - microbiology; macropinocytosis; mice; Microbiology in the medical area; Mikrobiologi inom det medicinska området; mouse stomach; mucus layers; multidisciplinary; necrotizing enterocolitis; newborn; Organ Specificity; paneth cells; Paneth Cells - cytology; Paneth Cells - microbiology; Rats; Science; Science & Technology - Other Topics; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-00123-w

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.