title: Enteropathogenic Escherichia coli inhibits butyrate uptake in Caco-2 cells by altering the apical membrane MCT1 level.
abstract: Enteropathogenic Escherichia coli (EPEC), a food-borne human pathogen, is responsible for infantile diarrhea, especially in developing countries. The pathophysiology of EPEC-induced diarrhea, however, is not completely understood. Our recent studies showed modulation of Na+/H+ and Cl-/HCO3- exchange activities in Caco-2 cells in response to EPEC infection. We hypothesized that intestinal short-chain fatty acid absorption mediated by monocarboxylate transporter 1 (MCT1) might also be altered by EPEC infection. The aim of the current studies was to examine the effect of EPEC infection on butyrate uptake. Caco-2 cells were infected with wild-type EPEC, various mutant strains, or nonpathogenic E. coli HS4, and [14C]butyrate uptake was determined. EPEC, but not nonpathogenic E. coli, significantly decreased butyrate uptake. Infection of cells with strains harboring mutations in escN, which encodes a putative ATPase for the EPEC type III secretion system (TTSS), or in the espA, espB, or espD genes encoding structural components of the TTSS, had no effect on butyrate uptake, indicating the TTSS dependence. On the other hand, strains with mutations in the effector protein genes espF, espG, espH, and map inhibited butyrate uptake, similar to the wild-type EPEC. Surface expression of MCT1 decreased considerably after EPEC but not after nonpathogenic E. coli infection. In conclusion, our studies demonstrate inhibition of MCT1-mediated butyrate uptake in Caco-2 cells in response to EPEC infection. This inhibition was dependent on a functional TTSS and the structural proteins EspA, -B, and -D of the translocation apparatus.
authors.affiliation: Department of Medicine, University of Illinois at Chicago and Jesse Brown Veteran Affairs Medical Center, 820 South Damen Ave., Chicago, IL 60612, USA.
authors.forename: Alip
authors.initials: A
authors.lastname: Borthakur
authors.forename: Ravinder K
authors.initials: RK
authors.lastname: Gill
authors.forename: Kim
authors.initials: K
authors.lastname: Hodges
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Ramaswamy
authors.forename: Gail
authors.initials: G
authors.lastname: Hecht
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Dudeja
mesh_terms: D001692:Biological Transport; D002087:Butyrates / Q000378:metabolism* / Q000494:pharmacology; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D013997:Time Factors; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D002087:Butyrates; D029968:Escherichia coli Proteins; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1