title: Role of host xanthine oxidase in infection due to enteropathogenic and Shiga-toxigenic Escherichia coli.
abstract: Xanthine oxidase (XO), also known as xanthine oxidoreductase, has long been considered an important host defense molecule in the intestine and in breastfed infants. Here, we present evidence that XO is released from and active in intestinal tissues and fluids in response to infection with enteropathogenic Escherichia coli (EPEC) and Shiga-toxigenic E. coli (STEC), also known as enterohemorrhagic E. coli (EHEC). XO is released into intestinal fluids in EPEC and STEC infection in a rabbit animal model. XO activity results in the generation of surprisingly high concentrations of uric acid in both cultured cell and animal models of infection. Hydrogen peroxide (H(2)O(2)) generated by XO activity triggered a chloride secretory response in intestinal cell monolayers within minutes but decreased transepithelial electrical resistance at 6 to 22 h. H(2)O(2) generated by XO activity was effective at killing laboratory strains of E. coli, commensal microbiotas, and anaerobes, but wild-type EPEC and STEC strains were 100 to 1,000 times more resistant to killing or growth inhibition by this pathway. Instead of killing pathogenic bacteria, physiologic concentrations of XO increased virulence by inducing the production of Shiga toxins from STEC strains. In vivo, exogenous XO plus the substrate hypoxanthine did not protect and instead worsened the outcome of STEC infection in the rabbit ligated intestinal loop model of infection. XO released during EPEC and STEC infection may serve as a virulence-inducing signal to the pathogen and not solely as a protective host defense.
authors: Department of Medicine, Division of Infectious Diseases, University at Buffalo, Buffalo, New York, USA. jcrane@buffalo.edu
authors: John K
authors: JK
authors: Crane
authors: Tonniele M
authors: TM
authors: Naeher
authors: Jacqueline E
authors: JE
authors: Broome
authors: Edgar C
authors: EC
authors: Boedeker
mesh_terms: D000818:Animals; D012634:Bodily Secretions / Q000201:enzymology; D002460:Cell Line; D004195:Disease Models, Animal; D054308:Enteropathogenic Escherichia coli / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D054884:Host-Pathogen Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007422:Intestines / Q000201:enzymology / Q000276:immunology; D011817:Rabbits; D054323:Shiga-Toxigenic Escherichia coli / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*; D014527:Uric Acid / Q000378:metabolism; D014774:Virulence / Q000187:drug effects; D014969:Xanthine Oxidase / Q000276:immunology / Q000378:metabolism*
chemical_list: D014527:Uric Acid; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase