An Outer Membrane Receptor of Neisseria meningitidis Involved in Zinc Acquisition with Vaccine Potential

PLoS Pathogens

Martine P. Bos¹  Ingrid Schilders¹  Ilse Jongerius¹  Jan Tommassen¹  Natasja de Kok¹  Michiel Stork¹  Jan T. Poolman²  Vincent E. Weynants² 

[1] Department of Molecular Microbiology, Utrecht University, Utrecht, The Netherlands;GlaxoSmithKline Biologicals, Rixensart, Belgium

关键词: Zinc;    Neisseria meningitidis;    Outer membrane proteins;    Vaccines;    Antibodies;    Membrane receptor signaling;    Gram negative bacteria;    Sequence alignment;   

DOI  :  10.1371/journal.ppat.1000969

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY