An outer membrane receptor of Neisseria meningitidis involved in zinc acquisition with vaccine potential.
Since the concentration of free iron in the human host is low, efficient iron-acquisition mechanisms constitute important virulence factors for pathogenic bacteria. In Gram-negative bacteria, TonB-dependent outer membrane receptors are implicated in iron acquisition. It is far less clear how other metals that are also scarce in the human host are transported across the bacterial outer membrane. With the aim of identifying novel vaccine candidates, we characterized in this study a hitherto unknown receptor in Neisseria meningitidis. We demonstrate that this receptor, designated ZnuD, is produced under zinc limitation and that it is involved in the uptake of zinc. Upon immunization of mice, it was capable of inducing bactericidal antibodies and we could detect ZnuD-specific antibodies in human convalescent patient sera. ZnuD is highly conserved among N. meningitidis isolates and homologues of the protein are found in many other Gram-negative pathogens, particularly in those residing in the respiratory tract. We conclude that ZnuD constitutes a promising candidate for the development of a vaccine against meningococcal disease for which no effective universal vaccine is available. Furthermore, the results suggest that receptor-mediated zinc uptake represents a novel virulence mechanism that is particularly important for bacterial survival in the respiratory tract.
Stork
Michiel
M
Department of Molecular Microbiology, Utrecht University, Utrecht, The Netherlands.
Bos
Martine P
MP
Jongerius
Ilse
I
de Kok
Natasja
N
Schilders
Ingrid
I
Weynants
Vincent E
VE
Poolman
Jan T
JT
Tommassen
Jan
J
D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007114:Immunization; D022401:Meningococcal Vaccines / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics* / Q000472:pathogenicity; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D022401:Meningococcal Vaccines; C553584:ZnuD protein, Neisseria meningitidis; C114819:Zur protein, E coli; D015032:Zinc