Biochemical evidence for a conserved interaction between bacterial transferrin binding protein A and transferrin binding protein B.

As an adaptation to the iron-restricted environment of the host, some bacterial pathogens possess iron acquisition pathways mediated by surface receptors that specifically bind transferrin from the host. The receptor is composed of two receptor proteins, TbpA and TbpB, which are both capable of binding to transferrin. Previous studies have demonstrated that affinity isolation of TbpB from Neisseria meningitidis or Haemophilus influenzae with immobilized human transferrin required the homologous TbpA, implicating a TbpA-TbpB interaction. In this study, we demonstrated that TbpA from either species can facilitate isolation of either TbpB, indicating that the TbpA-TbpB interaction is conserved within these species. Extension of these studies to veterinary pathogens in which a TbpA-Tf complex is used to affinity isolate heterologous TbpBs, demonstrated an interaction between the receptor proteins from N. meningitidis and Actinobacillus pleuropneumoniae. Further delineation of the TbpA-TbpB-transferrin interaction with recombinant chimeric N. meningitidis/A. pleuropneumoniae TbpBs has identified a region encoded by the first 1/4 of the tbpB gene which is involved in Tf binding.