Enteropathogenic Escherichia coli (EPEC) infection inhibits intestinal vitamin C transporter function and expression: in vitro and in vivo studies

Abstract

Enteropathogenic Escherichia coli (EPEC) is a food‐borne pathogen and causes enteric illnesses in children. EPEC infection is often associated with malnutrition of the host, especially in individuals experiencing severe and prolonged infection, and/or in those who are nutritionally compromised. While EPEC infection impacts nutrient transporter function and expression in intestinal epithelial cells, to date the consequences of EPEC infection on intestinal absorption of ascorbic acid (AA) are not known. Therefore, we investigated this issue using human intestinal epithelial Caco‐2 cells (in vitro) and mouse (in vivo) models. Infecting Caco‐2 cells with EPEC (WT) markedly inhibited AA uptake. EPEC mutants (ΔescN, ΔespA, ΔespB and ΔespD) did not affect AA uptake, whereas ΔespF and ΔespG/G2 mutants significantly inhibited AA uptake in Caco‐2 cells. Further, we observed significantly reduced expression of both hSVCT1 and hSVCT2 protein and mRNA levels upon infection. Similarly, infecting mice with EPEC (WT) significantly inhibited AA uptake and also reduced the expression of both mSVCT1 and mSVCT2 protein and mRNA levels in jejunum and colon. Studies have shown that epigenetic mechanisms (microRNA) play a role in mediating responses to bacterial infection in the intestine. Therefore, we determined miR103a, miR141 and miR200a expression levels, which were recently shown to regulate SVCT1 and SVCT2. Data from in vitro and in vivo models showed that all three microRNAs were up‐regulated significantly upon EPEC infection. In addition, expression of the accessory protein human glyoxalate reductase/hydroxypyruvate reductase (hGRHPR), which regulates the SVCT1 function, was also markedly decreased by EPEC in both models. These findings suggest that in intestinal epithelial cells, EPEC infection markedly inhibits AA uptake via dysregulation of both SVCT1 and SVCT2 expression.Support or Funding InformationSupported by NIH grants DK 107474, DK 58057, DK 56057, MH108154, GM088790, and a grant from the DVA