Birchenough, GMH; (2013) Analysis of intestinal factors contributing to the age-dependency of systemic neuropathogenic Escherichia coli K1 infection in the neonatal rat. Doctoral thesis , UCL (University College London).

Preview

PDF Thesis Total.pdf Available under License : See the attached licence file. Download (7MB)

Abstract

Infections by encapsulated bacteria are a major cause of neonatal mortality. Escherichia coli are isolated in a significant proportion of these infections with 80-85% of isolates expressing the K1 polysaccharide capsular antigen. Systemic E. coli K1 infection is age-dependent, the basis of which is likely the capacity of the pathogen to translocate from the gastrointestinal (GI) tract into the bloodstream. This step in pathogenesis is poorly characterized. Post-partum development of the GI microbial population (microbiota) and host tissue may modulate susceptibility to E. coli K1. Two-day old (P2) neonatal rats were susceptible to infection with E. coli K1 strain A192PP, whereas P9 neonates were refractive. This variation was not caused by the capacity of the pathogen to colonize the GI tract. The P2-P9 microbiota was significantly different to that of the adult, but very little variation occurred between the neonatal groups examined. Suppression of the P9 microbiota using antibiotic treatment did not increase susceptibility E. coli K1. A substantial degree of developmental GI tissue expression was observed over P2-P9, including the up-regulation of components of the small intestinal (α-defensin peptides Defa24 and Defa-rs1) and colonic (trefoil factor peptide Tff2) mucus barrier. Colonization with E. coli K1 was dysregulated Tff2 expression in P2 tissues, likely due to IL-1β and NFκB signalling, and was accompanied by a decrease in the mucin Muc2. Alpha-defensin expression was up-regulated in P9 tissues. These results indicated that the intestinal barrier function of the P9 GI tract is more developed than the P2 equivalent. E. coli K1 colonization may compromise the development of the colonic mucus barrier in P2 neonates. This supports the hypothesis that the developmental state of the GI tissue, but not the microbiota, modulates susceptibility to systemic E. coli K1 infection.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as XMLCSVJSON

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item