title: Direct ROS scavenging activity of CueP from Salmonella enterica serovar Typhimurium.
abstract: Salmonella enterica serovar Typhimurium (S. Typhimurium) is an intracellular pathogen that has evolved to survive in the phagosome of macrophages. The periplasmic copper-binding protein CueP was initially known to confer copper resistance to S. Typhimurium. Crystal structure and biochemical studies on CueP revealed a putative copper binding site surrounded by the conserved cysteine and histidine residues. A recent study reported that CueP supplies copper ions to periplasmic Cu, Zn-superoxide dismutase (SodCII) at a low copper concentration and thus enables the sustained SodCII activity in the periplasm. In this study, we investigated the role of CueP in copper resistance at a high copper concentration. We observed that the survival of a cueP-deleted strain of Salmonella in macrophage phagosome was significantly reduced. Subsequent biochemical experiments revealed that CueP specifically mediates the reduction of copper ion using electrons released during the formation of the disulfide bond. We observed that the copper ion-mediated Fenton reaction in the presence of hydrogen peroxide was blocked by CueP. This study provides insight into how CueP confers copper resistance to S. Typhimurium in copper-rich environments such as the phagosome of macrophages.
authors.affiliation: College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 609-735, Korea.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Yoon
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Yeom
authors.forename: Jin-Sik
authors.initials: JS
authors.lastname: Kim
authors.forename: Si-Hyeon
authors.initials: SH
authors.lastname: Um
authors.forename: Inseong
authors.initials: I
authors.lastname: Jo
authors.forename: Kangseok
authors.initials: K
authors.lastname: Lee
authors.forename: Yong-Hak
authors.initials: YH
authors.lastname: Kim
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Ha
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003300:Copper / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D010588:Phagosomes / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012480:Salmonella Infections / Q000097:blood / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D017382:Reactive Oxygen Species; C023548:copper-binding protein; D003300:Copper; D006861:Hydrogen Peroxide