title: Transferrin-iron uptake by Gram-negative bacteria.
abstract: Members of the families Neisseriaceae, Pasteurellaceae and Moraxellaceae are capable of transferrin-iron acquisition in the absence of siderophore production. They do so via expression of a bi-partite receptor composed of two dissimilar proteins, TbpA and TbpB. Both proteins are surface exposed, iron-regulated and capable of binding transferrin. However, other physiochemical, antigenic, and immunogenic characteristics of the proteins are quite distinct. TbpB is a lipoprotein, which like the mammalian transferrin receptor is capable if discriminating between apo- and holo-transferrin. Expression of TbpB is not essential for transferrin-iron uptake, and in rare situations, the gene that encodes this protein is not linked to the gene encoding the second component. TbpA is a member of a family of TonB-dependent transporters, others of which accomplish ferric-siderophore and vitamin B12 uptake at the expense of a proton gradient across the cytoplasmic membrane. However, unlike the other TonB-dependent receptors where vitamins or ferric-siderophores are wholly internalized, the bacterial transferrin receptor must remove iron from transferrin at the cell surface. This review focuses on the structure-function relationships in the transferrin-binding proteins, their sequence and antigenic diversity, and the mechanisms by which they accomplish transferrin-iron uptake. The contribution of these proteins to pathogenesis and vaccine development based on TbpA and TbpB are also discussed.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Virginia campus, Virginia Commonwealth University, Richmond, VA 23298-0678, USA. cncornel@hsc.vcu.edu
authors.forename: Cynthia Nau
authors.initials: CN
authors.lastname: Cornelissen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D014168:Transferrin / Q000378:metabolism*
chemical_list: D033862:Iron-Binding Proteins; D014168:Transferrin; D007501:Iron