Identification and characterisation of a novel conserved outer membrane protein from Neisseria meningitidis

Abstract

We have identified a homologue of the adhesin AIDA-I of Escherichia coli in Neisseria meningitidis. This gene was designated nhhA (Neisseria hia homologue), as analysis of the complete coding sequence revealed that it is more closely related to the adhesins Hia and Hsf of Haemophilus influenzae. The sequence of nhhA was determined from 10 strains, and found to be highly conserved. Studies of the localisation by Western immunoblot analysis of total cell proteins and outer membrane complex preparations and by immunogold electron microscopy revealed that NhhA is located in the outer membrane. A strain survey showed that nhhA is present in 85/85 strains of N. meningitidis representative of all the major disease-associated serogroups, based on Southern blot analysis. It is expressed in the majority of strains tested by Western immunoblot.

Autotransported Serine Protease A of Neisseria meningitidis : an Immunogenic, Surface-Exposed Outer Membrane, and Secreted Protein

“…The characteristic structure of autotransporter proteins and the secretion mechanism have been reviewed elsewhere (15,17). Autotransporter proteins, possessing a diverse array of N-terminal "functional" domains, have been reported in many gram-negative organisms (1,2,5,6,9,10,12,13,(23)(24)(25)(29)(30)(31). Typically, these proteins exhibit virulence-associated functions, such as adhesion, cytotoxicity, serum resistance, and proteolysis (14).…”

Meningococcal Outer Membrane Protein NhhA Is Essential for Colonization and Disease by Preventing Phagocytosis and Complement Attack

“…NhhA is a surface-exposed outer membrane protein which exists among all tested pathogenic Neisseria strains (26,27). The high conservation of NhhA among a broad range of meningococcal strains implies a critical role in the bacterial pathophysiology.…”

“…NhhA, Neisseria Hia/Hsf homologue, is an outer membrane protein homologous to the Hia and Hsf adhesins of Haemophilus influenzae (14,26). These proteins exhibit divergent functional properties and often contribute to bacterial adherence, invasion, microcolony formation (12,15), transepithelial trafficking (16), or serum resistance (2).…”

“…The meningococcal NhhA protein is composed of 590 amino acids and is a trimeric autotransporter adhesin that is present in all tested meningococcal strains. The C-terminal part of the protein is highly conserved, whereas the N-terminal part contains both variable and conserved regions (26,27,31). In a reversed vaccinology approach, NhhA (also called GNA0992) was identified as a surface-exposed antigen able to induce a bactericidal antibody response (27).…”

Mechanisms of Protein Export across the Bacterial Outer Membrane

“…Studies with these ATs supported the formation of a trimeric 12-stranded ␤-barrel in which each monomer contributes four transmembrane ␤-strands (54,56,66). All these proteins are characterized by a very short translocator domain ϳ70 residues in length (33,56,66).…”