Two pathways for ATP release from host cells in enteropathogenic Escherichia coli infection.
We previously reported that enteropathogenic Escherichia coli (EPEC) infection triggered a large release of ATP from the host cell that was correlated with and dependent on EPEC-induced killing of the host cell. We noted, however, that under some circumstances, EPEC-induced ATP release exceeded that which could be accounted for on the basis of host cell killing. For example, EPEC-induced ATP release was potentiated by noncytotoxic agents that elevate host cell cAMP, such as forskolin and cholera toxin, and by exposure to hypotonic medium. These findings and the performance of the EPEC espF mutant led us to hypothesize that the CFTR plays a role in EPEC-induced ATP release that is independent of cell death. We report the results of experiments using specific, cell-permeable CFTR activators and inhibitors, as well as transfection of the CFTR into non-CFTR-expressing cell lines, which incriminate the CFTR as a second pathway for ATP release from host cells. Increased ATP release via CFTR is not accompanied by an increase in EPEC adherence to transfected cells. The CFTR-dependent ATP release pathway becomes activated endogenously later in EPEC infection, and this activation is mediated, at least in part, by generation of extracellular adenosine from the breakdown of released ATP.
Crane
John K
JK
Department of Medicine, Division of Infectious Diseases, University of Buffalo, Rm. 317, Biomedical Research Bldg., 3435 Main St., Buffalo, NY 14214, USA. jcrane@buffalo.edu
Naeher
Tonniele M
TM
Choudhari
Shilpa S
SS
Giroux
Elisa M
EM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D002277:Carcinoma / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004847:Epithelial Cells; D004926:Escherichia coli / Q000472:pathogenicity* / Q000502:physiology*; D004927:Escherichia coli Infections / Q000503:physiopathology*; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D014407:Tumor Cells, Cultured
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate