Title: Decreased expression of colonic Slc26a3 and carbonic anhydrase iv as a cause of fatal infectious diarrhea in mice.
Authors: Borenshtein, Diana; Schlieper, Katherine A; Rickman, Barry H; Chapman, Jeannie M; Schweinfest, Clifford W; Fox, James G; Schauer, David B
Published In Infect Immun, (2009 Sep)
Abstract: Citrobacter rodentium causes epithelial hyperplasia and colitis and is used as a model for enteropathogenic and enterohemorrhagic Escherichia coli infections. Little or no mortality develops in most inbred strains of mice, but C3H and FVB/N mice exhibit fatal outcomes of infection. Here we test the hypothesis that decreased intestinal transport activity during C. rodentium infection results in fatality in C3H/HeOu and FVB/N mice. Susceptible strains were compared to resistant C57BL/6 mice and to inbred strains SWR and SJL of Swiss origin, which have not been previously characterized for outcomes of C. rodentium infection. Mortality in susceptible strains C3H/HeOu and FVB/N was associated with significant fluid loss in feces, a remarkable downregulation of Slc26a3 and carbonic anhydrase IV (CAIV) message and protein expression, retention of chloride in stool, and hypochloremia, suggesting defects in intestinal chloride absorption. SWR, SJL, and C57BL/6 mice were resistant and survived the infection. Fluid therapy fully prevented mortality in C3H/HeOu and FVB/N mice without affecting clinical disease. Common pathogenic mechanisms, such as decreased levels of expression of Slc26a3 and CAIV, affect intestinal ion transport in C. rodentium-infected FVB and C3H mice, resulting in profound electrolyte loss, dehydration, and mortality. Intestinal chloride absorption pathways are likely a potential target for the treatment of infectious diarrhea.
PubMed ID: 19546193
MeSH Terms: Animals; Antiporters/genetics; Antiporters/physiology*; Bacterial Translocation; Carbonic Anhydrase IV/genetics; Carbonic Anhydrase IV/physiology*; Chlorides/metabolism; Citrobacter rodentium/pathogenicity*; Colon/metabolism*; Diarrhea/etiology*; Disease Susceptibility; Enterobacteriaceae Infections/complications*; Enterobacteriaceae Infections/mortality; Enterobacteriaceae Infections/pathology; Female; Fluid Therapy; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Species Specificity