title: The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron-replete and iron-depleted conditions.
abstract: Neisseria gonorrhoeae produces two transferrin binding proteins, TbpA and TbpB, which together enable efficient iron transport from human transferrin. We demonstrate that expression of the tbp genes is controlled by MisR, a response regulator in the two-component regulatory system that also includes the sensor kinase MisS. The tbp genes were up-regulated in the misR mutant under iron-replete conditions but were conversely down-regulated in the misR mutant under iron-depleted conditions. The misR mutant was capable of transferrin-iron uptake at only 50% of wild-type levels, consistent with decreased tbp expression. We demonstrate that phosphorylated MisR specifically binds to the tbpBA promoter and that MisR interacts with five regions upstream of the tbpB start codon. These analyses confirm that MisR directly regulates tbpBA expression. The MisR binding sites in the gonococcus are only partially conserved in Neisseria meningitidis, which may explain why tbpBA was not MisR-regulated in previous studies using this related pathogen. This is the first report of a trans-acting protein factor other than Fur that can directly contribute to gonococcal tbpBA regulation.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Kandler
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University Health System, Richmond, Virginia.
authors.forename: Rosuany Vélez
authors.initials: RV
authors.lastname: Acevedo
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University Health System, Richmond, Virginia.
authors.forename: Mary Kathryne
authors.initials: MK
authors.lastname: Dickinson
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University Health System, Richmond, Virginia.
authors.forename: Devin R
authors.initials: DR
authors.lastname: Cash
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia.|Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia.|Department of Veterans Affairs Medical Center, Laboratories of Microbial Pathogenesis, Decatur, Georgia.
authors.forename: William M
authors.initials: WM
authors.lastname: Shafer
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University Health System, Richmond, Virginia. cynthia.cornelissen@vcuhealth.org.
authors.forename: Cynthia Nau
authors.initials: CN
authors.lastname: Cornelissen
mesh_terms: D001665:Binding Sites; D007501:Iron / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D033881:Transferrin-Binding Protein A / Q000235:genetics* / Q000378:metabolism; D033882:Transferrin-Binding Protein B / Q000235:genetics* / Q000378:metabolism
chemical_list: D015534:Trans-Activators; D014168:Transferrin; D033881:Transferrin-Binding Protein A; D033882:Transferrin-Binding Protein B; D007501:Iron