Transferrin-iron uptake by Gram-negative bacteria.
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.
Cornelissen
Cynthia Nau
CN
Department of Microbiology and Immunology, Medical College of Virginia campus, Virginia Commonwealth University, Richmond, VA 23298-0678, USA. cncornel@hsc.vcu.edu
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*
D033862:Iron-Binding Proteins; D014168:Transferrin; D007501:Iron