title: Zinc protects against Shiga-toxigenic Escherichia coli by acting on host tissues as well as on bacteria.
abstract: BACKGROUND
  Zinc supplements can treat or prevent enteric infections and diarrheal disease. Many articles on zinc in bacteria, however, highlight the essential nature of this metal for bacterial growth and virulence, suggesting that zinc should make infections worse, not better. To address this paradox, we tested whether zinc might have protective effects on intestinal epithelium as well as on the pathogen.
  
  
  RESULTS
  Using polarized monolayers of T84 cells we found that zinc protected against damage induced by hydrogen peroxide, as measured by trans-epithelial electrical resistance. Zinc also reduced peroxide-induced translocation of Shiga toxin (Stx) across T84 monolayers from the apical to basolateral side. Zinc was superior to other divalent metals to (iron, manganese, and nickel) in protecting against peroxide-induced epithelial damage, while copper also showed a protective effect.The SOS bacterial stress response pathway is a powerful regulator of Stx production in STEC. We examined whether zinc's known inhibitory effects on Stx might be mediated by blocking the SOS response. Zinc reduced expression of recA, a reliable marker of the SOS. Zinc was more potent and more efficacious than other metals tested in inhibiting recA expression induced by hydrogen peroxide, xanthine oxidase, or the antibiotic ciprofloxacin. The close correlation between zinc's effects on recA/SOS and on Stx suggested that inhibition of the SOS response is one mechanism by which zinc protects against STEC infection.
  
  
  CONCLUSIONS
  Zinc's ability to protect against enteric bacterial pathogens may be the result of its combined effects on host tissues as well as inhibition of virulence in some pathogens. Research focused solely on the effects of zinc on pathogenic microbes may give an incomplete picture by failing to account for protective effects of zinc on host epithelia.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University at Buffalo, Room 317 Biomedical Research Bldg, 3435 Main St, Buffalo, NY 14214, USA. jcrane@buffalo.edu.
authors.forename: John K
authors.initials: JK
authors.lastname: Crane
authors.forename: Jackie E
authors.initials: JE
authors.lastname: Broome
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Reddinger
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Werth
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000517:prevention & control*; D006801:Humans; D018384:Oxidative Stress; D013014:SOS Response, Genetics / Q000187:drug effects; D054323:Shiga-Toxigenic Escherichia coli / Q000187:drug effects*; D013312:Stress, Physiological; D015032:Zinc / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015032:Zinc