title: Reversible inhibition of Chlamydia trachomatis infection in epithelial cells due to stimulation of P2X(4) receptors.
abstract: Bacterial infections of the mucosal epithelium are a major cause of human disease. The prolonged presence of microbial pathogens stimulates inflammation of the local tissues, which leads to changes in the molecular composition of the extracellular milieu. A well-characterized molecule that is released to the extracellular milieu by stressed or infected cells is extracellular ATP and its ecto-enzymatic degradation products, which function as signaling molecules through ligation of purinergic receptors. There has been little information, however, on the effects of the extracellular metabolites on bacterial growth in inflamed tissues. Millimolar concentrations of ATP have been previously shown to inhibit irreversibly bacterial infection through ligation of P2X(7) receptors. We show here that the proinflammatory mediator, ATP, is released from Chlamydia trachomatis-infected epithelial cells. Moreover, further stimulation of the infected cells with micromolar extracellular ADP or ATP significantly impairs the growth of the bacteria, with a profile characteristic of the involvement of P2X(4) receptors. A specific role for P2X(4) was confirmed using cells overexpressing P2X(4). The chlamydiae remain viable and return to normal growth kinetics after removal of the extracellular stimulus, similar to responses previously described for persistence of chlamydial infection.
authors.affiliation: Molecular Cell Biology and Health Sciences Research Institute, University of California, Merced, California, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Pettengill
authors.forename: Camila
authors.initials: C
authors.lastname: Marques-da-Silva
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Avila
authors.forename: Suellen
authors.initials: S
authors.lastname: d'Arc dos Santos Oliveira
authors.forename: Verissa W
authors.initials: VW
authors.lastname: Lam
authors.forename: Ikechukwu
authors.initials: I
authors.lastname: Ollawa
authors.forename: Ali A
authors.initials: AA
authors.lastname: Abdul Sater
authors.forename: Robson
authors.initials: R
authors.lastname: Coutinho-Silva
authors.forename: Georg
authors.initials: G
authors.lastname: Häcker
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D002690:Chlamydia Infections / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000382:microbiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D058848:Receptors, Purinergic P2X4 / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D058848:Receptors, Purinergic P2X4; D000255:Adenosine Triphosphate