an outer membrane receptor of neisseria meningitidis involved in zinc acquisition with vaccine potential脑膜炎奈瑟菌的外膜受体参与锌与疫苗潜在的收购.pdfVIP

An Outer Membrane Receptor of Neisseria meningitidis Involved in Zinc Acquisition with Vaccine Potential 1. 1. 1 1 1 Michiel Stork , Martine P. Bos , Ilse Jongerius , Natasja de Kok , Ingrid Schilders , Vincent E. 2 2 1 Weynants , Jan T. Poolman , Jan Tommassen * 1 Department of Molecular Microbiology, Utrecht University, Utrecht, The Netherlands, 2 GlaxoSmithKline Biologicals, Rixensart, Belgium Abstract 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