title: Role of copper efflux in pneumococcal pathogenesis and resistance to macrophage-mediated immune clearance.
abstract: In bacteria, the intracellular levels of metals are mediated by tightly controlled acquisition and efflux systems. This is particularly true of copper, a trace element that is universally toxic in excess. During infection, the toxic properties of copper are exploited by the mammalian host to facilitate bacterial clearance. To better understand the role of copper during infection, we characterized the contribution of the cop operon to copper homeostasis and virulence in Streptococcus pneumoniae. Deletion of either the exporter, encoded by copA, or the chaperone, encoded by cupA, led to hypersensitivity to copper stress. We further demonstrated that loss of the copper exporter encoded by copA led to decreased virulence in pulmonary, intraperitoneal, and intravenous models of infection. Deletion of copA resulted in enhanced macrophage-mediated bacterial clearance in vitro. The attenuation phenotype of the copA mutant in the lung was found to be dependent on pulmonary macrophages, underscoring the importance of copper efflux in evading immune defenses. Overall, these data provide insight into the role of the cop operon in pneumococcal pathogenesis.
authors: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Michael D L
authors: MD
authors: Johnson
authors: University of Illinois Urbana-Champaign, Department of Microbiology, Urbana, Illinois, USA.
authors: Thomas E
authors: TE
authors: Kehl-Fie
authors: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Roger
authors: R
authors: Klein
authors: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Jacqueline
authors: J
authors: Kelly
authors: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Corinna
authors: C
authors: Burnham
authors: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Beth
authors: B
authors: Mann
authors: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA jason.rosch@stjude.org.
authors: Jason W
authors: JW
authors: Rosch
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000235:genetics / Q000473:pathology; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D002460:Cell Line; D003300:Copper / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000378:metabolism; D011008:Pneumococcal Infections / Q000235:genetics / Q000473:pathology*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; C071263:CopA protein, Bacteria; D018832:Molecular Chaperones; D003300:Copper