title: Neisseria gonorrhoeae requires expression of TonB and the putative transporter TdfF to replicate within cervical epithelial cells.
abstract: Neisseria gonorrhoeae has evolved a repertoire of iron acquisition systems that facilitate essential iron uptake in the human host. Acquisition of iron requires both the energy-harnessing cytoplasmic membrane protein, TonB, as well as specific outer membrane TonB-dependent transporters (TdTs.) Survival within host epithelial cells is important to the pathogenesis of gonococcal disease and may contribute to the persistence of infection. However, the mechanisms by which gonococci acquire iron within this intracellular niche are not currently understood. In this study, we investigated the survival of gonococcal strain FA1090 within ME180 human cervical epithelial cells with respect to high affinity iron acquisition. Intracellular survival was dependent upon iron supplied by the host cell. TonB was expressed in the host cell environment and this protein was critical to gonococcal intracellular survival. Furthermore, expression of the characterized outer membrane transporters TbpA, FetA and LbpA and putative transporters TdfG, TdfH and TdfJ were not necessary for intracellular survival. Conversely, intracellular survival was dependent on expression of the putative transporter, TdfF. Expression of TdfF was detected in the presence of epithelial cell culture media containing fetal bovine serum. Expression was further modulated by iron availability. To our knowledge, this study is the first to demonstrate the specific requirement for a single iron transporter in the survival of a bacterial pathogen within host epithelial cells.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Hagen
authors.forename: Cynthia Nau
authors.initials: CN
authors.lastname: Cornelissen
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D002584:Cervix Uteri / Q000382:microbiology*; D003470:Culture Media; D004269:DNA, Bacterial; D003676:Deferoxamine / Q000378:metabolism; D004847:Epithelial Cells; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000254:growth & development / Q000502:physiology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D003470:Culture Media; D004269:DNA, Bacterial; D007502:Iron Chelating Agents; D008565:Membrane Proteins; C435216:TdfF protein, Neisseria; C057616:tonB protein, Bacteria; D007501:Iron; D003676:Deferoxamine