title: Role of transferrin receptor from a Neisseria meningitidis tbpB isotype II strain in human transferrin binding and virulence.
abstract: Neisseria meningitidis acquires iron through the action of the transferrin (Tf) receptor, which is composed of the Tf-binding proteins A and B (TbpA and TbpB). Meningococci can be classified into isotype I and II strains depending on whether they harbor a type I or II form of TbpB. Both types of TbpB have been shown to differ in their genomic, biochemical, and antigenic properties. Here we present a comparative study of isogenic mutants deficient in either or both Tbps from the isotype I strain B16B6 and isotype II strain M982. We show that TbpA is essential in both strains for iron uptake and growth with iron-loaded human Tf as a sole iron source. No growth has also been observed for the TbpB- mutant of strain B16B6, as shown previously, whereas the growth of the analogous mutant in M982 was similar to that in the wild type. This indicates that TbpB in the latter strain plays a facilitating but not essential role in iron uptake, which has been observed previously in similar studies of other bacteria. These data are discussed in relation to the fact that isotype II strains represent more than 80% of serogroup B meningococcal strains. The contribution of both subunits in the bacterial virulence of strain M982 has been assessed in a murine model of bacteremia. Both the TbpB- TbpA- mutant and the TbpA- mutant are shown to be nonvirulent in mice, whereas the virulence of the TbpB- mutant is similar to that of the wild type.
authors.affiliation: Aventis Pasteur, 69280 Marcy l'Etoile, France. genevieve.renauld@aventis.com
authors.forename: Geneviève
authors.initials: G
authors.lastname: Renauld-Mongénie
authors.forename: David
authors.initials: D
authors.lastname: Poncet
authors.forename: Michèle
authors.initials: M
authors.lastname: Mignon
authors.forename: Sophie
authors.initials: S
authors.lastname: Fraysse
authors.forename: Christophe
authors.initials: C
authors.lastname: Chabanel
authors.forename: Bernard
authors.initials: B
authors.lastname: Danve
authors.forename: Tino
authors.initials: T
authors.lastname: Krell
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Quentin-Millet
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000276:immunology; D007501:Iron / Q000378:metabolism; D008589:Meningococcal Infections / Q000382:microbiology; D051379:Mice; D009154:Mutation; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D011817:Rabbits; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000276:immunology / Q000378:metabolism*; D033881:Transferrin-Binding Protein A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D033882:Transferrin-Binding Protein B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014774:Virulence
chemical_list: D007132:Immunoglobulin Isotypes; D011990:Receptors, Transferrin; D014168:Transferrin; D033881:Transferrin-Binding Protein A; D033882:Transferrin-Binding Protein B; D007501:Iron