Analysis of TbpA and TbpB functionality in defective mutants of Neisseria meningitidis.
Iron uptake analysis suggested that the Neisseria meningitidis transferrin (Tf) binding proteins, TbpA and TbpB, form only one type of receptor complex. Mutants defective in the synthesis of either TbpA or TbpB, but not defective in both proteins, can bind Tf, suggesting that both proteins are surface exposed and function in Tf binding. Also, iron uptake from Tf into the meningococci did not require the presence of both Tbps. The TbpB-defective mutant incorporated c. 37% of the iron taken up by the wild-type strain, but this was insufficient for bacterial growth. The TbpA-defective mutant incorporated c. 50% of the iron taken up by the wild-type strain and was able to grow with Tf as the only iron source. Mouse antibodies specific for TbpA were able to block c. 70% of the iron uptake from Tf in the wild-type strain, whereas they blocked only 22% of iron uptake in the TbpB-defective mutant and did not block uptake in the TbpA-defective strain. These results emphasise that TbpA should be considered in future vaccine trials in which iron-restricted proteins are to be included in the vaccine formulation.
Pintor
M
M
Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain.
Gómez
J A
JA
Ferrón
L
L
Ferreirós
C M
CM
Criado
M T
MT
D019138:Antibodies, Blocking / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007504:Iron Radioisotopes; D033862:Iron-Binding Proteins; D007700:Kinetics; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000032:analysis / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*; D033863:Transferrin-Binding Proteins
D019138:Antibodies, Blocking; D002352:Carrier Proteins; D007504:Iron Radioisotopes; D033862:Iron-Binding Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D033863:Transferrin-Binding Proteins; D007501:Iron