title: An ERp57-mediated disulphide exchange promotes the interaction between Burkholderia cenocepacia and epithelial respiratory cells.
abstract: Previous studies have demonstrated that extracellular glutathione reduces the ability of the Cystic Fibrosis pathogen Burkholderia cenocepacia to infect primary or immortalized epithelial respiratory cells. We report here that the adhesion and invasion ability of B. cenocepacia is limited also by thiol-oxidizing and disulphide-reducing agents and by protein disulfide isomerase (PDI) inhibitors. PDI inhibitors also reduce the proinflammatory response elicited by cells in response to Burkholderia. These findings indicate that a membrane-associated PDI catalyzes thiol/disulphide exchange reactions which favor bacterial infection. The combined use of selective PDI inhibitors, RNA silencing and specific antibodies identified ERp57 as a major PDI involved in the interaction between B. cenocepacia and epithelial cells. This study contributes to the elucidation of the Burkholderia pathogenic mechanisms by showing that this microorganism exploits a membrane-associated host protein to infect epithelial cells and identifies ERp57 as a putative pharmacological target for the treatment of Burkholderia lung infections.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Roma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pacello
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Roma, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: D'Orazio
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Roma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Battistoni
mesh_terms: D057508:Burkholderia cenocepacia / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020868:Gene Silencing; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D018836:Inflammation Mediators / Q000378:metabolism; D008954:Models, Biological; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000382:microbiology*
chemical_list: D016207:Cytokines; D004220:Disulfides; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human