title: Enteropathogenic Escherichia coli inhibits ileal sodium-dependent bile acid transporter ASBT.
abstract: Apical sodium-dependent bile acid transporter (ASBT) is responsible for the absorption of bile acids from the intestine. A decrease in ASBT function and expression has been implicated in diarrhea associated with intestinal inflammation. Whether infection with pathogenic microorganisms such as the enteropathogenic Escherichia coli (EPEC) affect ASBT activity is not known. EPEC is a food-borne enteric pathogen that translocates bacterial effector molecules via type three secretion system (TTSS) into host cells and is a major cause of infantile diarrhea. We investigated the effects of EPEC infection on ileal ASBT function utilizing human intestinal Caco2 cells and HEK-293 cells stably transfected with ASBT-V5 fusion protein (2BT cells). ASBT activity was significantly inhibited following 60 min infection with EPEC but not with nonpathogenic E. coli. Mutations in bacterial escN, espA, espB, and espD, the genes encoding for the elements of bacterial TTSS, ablated EPEC inhibitory effect on ASBT function. Furthermore, mutation in the bacterial BFP gene encoding for bundle-forming pili abrogated the inhibition of ASBT by EPEC, indicating the essential role for bacterial aggregation and the early attachment. The inhibition by EPEC was associated with a significant decrease in the V(max) of the transporter and a reduction in the level of ASBT on the plasma membrane. The inhibition of ASBT by EPEC was blocked in the presence of protein tyrosine phosphatase inhibitors. Our studies provide novel evidence for the alterations in the activity of ASBT by EPEC infection and suggest a possible effect for EPEC in influencing intestinal bile acid homeostasis.
authors.affiliation: Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Fadi
authors.initials: F
authors.lastname: Annaba
authors.forename: Zaheer
authors.initials: Z
authors.lastname: Sarwar
authors.forename: Ravinder K
authors.initials: RK
authors.lastname: Gill
authors.forename: Amit
authors.initials: A
authors.lastname: Ghosh
authors.forename: Seema
authors.initials: S
authors.lastname: Saksena
authors.forename: Alip
authors.initials: A
authors.lastname: Borthakur
authors.forename: Gail A
authors.initials: GA
authors.lastname: Hecht
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Dudeja
authors.forename: Waddah A
authors.initials: WA
authors.lastname: Alrefai
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D058947:Bacterial Secretion Systems / Q000235:genetics / Q000502:physiology; D018938:Caco-2 Cells; D054308:Enteropathogenic Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D058947:Bacterial Secretion Systems; C087863:EaeB protein, E coli; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; C102051:EspA protein, E coli; C474481:EspD protein, E coli; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; D012964:Sodium; D017027:Protein Tyrosine Phosphatases