Two transferrin-binding proteins, TbpA and TbpB are components of a surface-exposed, human transferrin receptor expressed by Neisseria gonorrhoeae. These proteins, in addition to gonococcal TonB are necessary for efficient utilization of transferrin-bound iron. Because the receptor is expressed by all gonococci and the protein components are well conserved, their potential as vaccine targets is being explored. The overall goal of the proposed study is to determine how the gonococcal transferrin receptor complex accomplishes iron intemalization and if the components of the receptor induce a protective immune response.
The specific aims of the proposal address the following questions:
Aim 1. What is the molecular mechanism by which the components of the transferrin receptor complex accomplish the three phases of transferrin-iron acquisition: Tf binding, iron removal, and iron transport? The goals of this aim are to probe the structure/function relationships in TbpA, TbpB and TonB using a combination of mutagenesis and biochemical characterization of receptor function. A detailed understanding of the mechanism of transferrin- iron transport will focus vaccine strategies on the functional relevance of particular epitopes.
Aim 2. What molecular mechanisms coordinately control expression of TbpA, TbpB and TonB? Characterization of the promoter and regulatory stimuli that impact expression of these proteins will lead to a better understanding of how optimal amounts of transferrin receptor components are achieved. Moreover, the optimized function of the receptor is a result of the coordinated expression of the individual components.
Aim 3. What are the biological activities of the anti-Tbp antibodies and are these antibodies protective? Antibody responses elicited against TbpA, TbpB and epitopes thereof, will be characterized following vaccination of laboratory animals. Selected antigens, combined with mucosal adjuvants,will befurther evaluated for their ability to elicit a protective immune response in mice.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IDM-A (02))
Program Officer
Hiltke, Thomas J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Virginia Commonwealth University
Schools of Medicine
United States
Zip Code
Jean, Sophonie; Juneau, Richard A; Criss, Alison K et al. (2016) Neisseria gonorrhoeae Evades Calprotectin-Mediated Nutritional Immunity and Survives Neutrophil Extracellular Traps by Production of TdfH. Infect Immun 84:2982-94
Kandler, Justin L; Acevedo, Rosuany Vélez; Dickinson, Mary Kathryne et al. (2016) The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron-replete and iron-depleted conditions. Mol Microbiol 102:137-51
Vélez Acevedo, Rosuany N; Ronpirin, Chalinee; Kandler, Justin L et al. (2014) Identification of regulatory elements that control expression of the tbpBA operon in Neisseria gonorrhoeae. J Bacteriol 196:2762-74
Noinaj, Nicholas; Cornelissen, Cynthia Nau; Buchanan, Susan K (2013) Structural insight into the lactoferrin receptors from pathogenic Neisseria. J Struct Biol 184:83-92
Noinaj, Nicholas; Buchanan, Susan K; Cornelissen, Cynthia Nau (2012) The transferrin-iron import system from pathogenic Neisseria species. Mol Microbiol 86:246-57
Banerjee, Sambuddha; Siburt, Claire J Parker; Mistry, Shreni et al. (2012) Evidence of Fe3+ interaction with the plug domain of the outer membrane transferrin receptor protein of Neisseria gonorrhoeae: implications for Fe transport. Metallomics 4:361-72
Cornelissen, Cynthia Nau; Hollander, Aimee (2011) TonB-Dependent Transporters Expressed by Neisseria gonorrhoeae. Front Microbiol 2:117
Hollander, Aimee; Mercante, Alexandra Dubon; Shafer, William M et al. (2011) The iron-repressed, AraC-like regulator MpeR activates expression of fetA in Neisseria gonorrhoeae. Infect Immun 79:4764-76
Strange, Heather R; Zola, Tracey A; Cornelissen, Cynthia Nau (2011) The fbpABC operon is required for Ton-independent utilization of xenosiderophores by Neisseria gonorrhoeae strain FA19. Infect Immun 79:267-78
Zola, Tracey A; Strange, Heather R; Dominguez, Nadia M et al. (2010) Type IV secretion machinery promotes ton-independent intracellular survival of Neisseria gonorrhoeae within cervical epithelial cells. Infect Immun 78:2429-37

Showing the most recent 10 out of 24 publications