title: Escherichia coli uropathogenic-specific protein, Usp, is a bacteriocin-like genotoxin.
abstract: BACKGROUND
  Bacterial genotoxins provoke DNA damage and carcinogenesis. The Escherichia coli uropathogenic-specific protein gene, usp, and its linked genes, imu1-3, are associated with strains from pyelonephritis, prostatitis, and bacteremia of urinary tract origin. While the Usp C-terminal domain exhibits similarity with DNase-like colicins and pyocins, its role and mechanisms of action, as well as those of the 3 associated proteins, is unknown.
  
  
  METHODS
  We isolated Usp and Imu1-3 and examined their activity on plasmid DNA, human umbilical vein endothelial cells, and human embryonic kidney cells (cell line HEK293). The affect of Usp and Imu1-3 was assessed by MTT and Comet assays, infection assays, caspase 3/7 activity, fluorescently labeled actin staining, and Western blotting.
  
  
  RESULTS
  Usp possesses DNase activity and, particularly when coapplied with Imu2, exhibits genotoxic activity in mammalian cells. Infection assays demonstrated that E. coli usp(+) imu1-3(+) affects the viability of mammalian cells, induces increased caspase 3/7 activity, and perturbs cell cytoskeleton structure.
  
  
  CONCLUSIONS
  Usp is a novel E. coli genotoxin active against mammalian cells. Optimal in vivo activity of Usp requires Imu2. Infection with E. coli usp(+) imu1-3(+) induces a response characteristic of apoptosis.
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Večna pot 111, 1000 Ljubljana, Slovenia.
authors.forename: Damijan
authors.initials: D
authors.lastname: Nipič
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Podlesek
authors.forename: Maruska
authors.initials: M
authors.lastname: Budič
authors.forename: Miha
authors.initials: M
authors.lastname: Črnigoj
authors.forename: Darja
authors.initials: D
authors.lastname: Žgur-Bertok
mesh_terms: D001430:Bacteriocins / Q000494:pharmacology* / Q000633:toxicity; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D003851:Deoxyribonucleases / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D009153:Mutagens / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D001430:Bacteriocins; D029968:Escherichia coli Proteins; D009153:Mutagens; C446159:USP protein, E coli; D003851:Deoxyribonucleases; D020169:Caspases
keywords: Escherichia coli; bacteriocin-like; genotoxin; uropathogenic specific protein