In this section
@article{McCarthy:2019:10.1128/iai.00878-18,
author = {McCarthy, AJ and Birchenough, GMH and Taylor, PW},
doi = {10.1128/iai.00878-18},
journal = {Infection and Immunity},
title = {Loss of Trefoil Factor 2 Sensitizes Rat Pups to Systemic Infection with the Neonatal Pathogen Escherichia coli K1},
url = {http://dx.doi.org/10.1128/iai.00878-18},
volume = {87},
year = {2019}
}
TY - JOUR
AB - <jats:title>ABSTRACT</jats:title><jats:p>Gastrointestinal (GI) colonization of 2-day-old (P2) rat pups with <jats:named-content content-type="genus-species">Escherichia coli</jats:named-content> K1 results in translocation of the colonizing bacteria across the small intestine, bacteremia, and invasion of the meninges, with animals frequently succumbing to lethal infection. Infection, but not colonization, is strongly age dependent; pups become progressively less susceptible to infection over the P2-to-P9 period. Colonization leads to strong downregulation of the gene encoding trefoil factor 2 (Tff2), preventing maturation of the protective mucus barrier in the small intestine. Trefoil factors promote mucosal homeostasis. We investigated the contribution of Tff2 to protection of the neonatal rat from <jats:named-content content-type="genus-species">E. coli</jats:named-content> K1 bacteremia and tissue invasion. Deletion of <jats:italic>tff2</jats:italic>, using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, sensitized P9 pups to <jats:named-content content-type="genus-species">E. coli</jats:named-content> K1 bacteremia. There were no differences between <jats:italic>tff2<jats:sup>−/</jats:sup></jats:italic><jats:sup>−</jats:sup> homozygotes and the wild type with regard to the dynamics of GI colonization. Loss of the capacity to elaborate Tff2 did not impact GI tract integrity or the thickness of the small-intestinal mucus layer but, in contrast to P9 wild-type pups, enabled <jats:named-content content-type="genus-species">E. coli</jats:named-content> K1 bacteria to gain access to epithelial surfaces in the distal region of the small intestine and exploit an intracellular route across the epithelial monolayer to enter the blood circulation via the mesenteric lymphatic system. Al
AU - McCarthy,AJ
AU - Birchenough,GMH
AU - Taylor,PW
DO - 10.1128/iai.00878-18
PY - 2019///
SN - 0019-9567
TI - Loss of Trefoil Factor 2 Sensitizes Rat Pups to Systemic Infection with the Neonatal Pathogen Escherichia coli K1
T2 - Infection and Immunity
UR - http://dx.doi.org/10.1128/iai.00878-18
VL - 87
ER -
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