[Show abstract][Hide abstract] ABSTRACT:
The outer membrane protects Gram-negative bacteria against harmful compounds from the environment. Nutrients usually pass this barrier by passive diffusion via pore-forming proteins. However, nutrients that are scarce in the environment are taken up via an active, receptor-mediated process. The vast majority of Gram-negative bacterial receptors described to date are involved in iron acquisition. Since free iron is scarce in the human host, these receptors constitute important virulence factors. In a search for putative vaccine components, we have characterized here a new receptor of Neisseria meningitidis, a resident of the nasopharynx that occasionally causes sepsis and meningitis. We show that expression of this receptor is induced under zinc limitation and that the protein is involved in the uptake of zinc. Homologues of this protein are present in many other Gram-negative pathogens, particularly in those residing in the respiratory tract, suggesting that receptor-mediated zinc acquisition is important for bacteria residing in this niche. We also found that the protein is highly conserved among N. meningitidis isolates and that it induces bactericidal antibodies upon immunization of mice. Therefore, the protein appears an excellent candidate for the development of a vaccine against N. meningitidis, for which no universal vaccine is available yet.