Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes

Pajón, Rolando; Yero, Daniel; Niebla, Olivia; Climent, Yanet; Sardiñas, Gretel; García, Duniesky Martinez; Perera, Yasser; Llanes, Alejandro; Delgado, Maité; Cobas, Karem; Caballero, Evelin; Taylor, Stephen; Brookes, Charlotte; Gorringe, Andrew

doi:10.1016/j.vaccine.2009.09.128

Cited by 22 publications

(11 citation statements)

References 71 publications

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“…Moreover we could substantiate these findings using whole-cell ELISA experiments similarly demonstrating BamC was surface exposed. In keeping with this finding, BamC (NlpB) has been identified as a prospective vaccine candidate for meningitis, selected in a high-throughput screen for antibodies protecting against Neisseria meningitidis infection 32 . Remarkably, this surface antigen incorporates both helix-grip domains as recognized by cell surface proteolysis.…”

Section: Discussionmentioning

confidence: 90%

Dynamic Association of BAM Complex Modules Includes Surface Exposure of the Lipoprotein BamC

Webb

Selkrig

Perry

et al. 2012

Journal of Molecular Biology

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The BAM complex drives assembly of β-barrel proteins into the outer membrane of gram-negative bacteria. It is composed of five subunits: BamA, BamB, BamC, BamD and BamE. We find that the BAM complex isolated from the outer membrane of Escherichia coli consists of a core complex of BamA:B:C:D:E and in addition, a BamA:B module and a BamC:D module. In the absence of BamC, these modules are destabilized resulting in increased protease susceptibility of BamD and BamB. While the N-terminus of BamC carries a highly conserved region crucial for stable interaction with BamD, immunofluorescence, immunoprecipitation and protease-sensitivity assays show that the C-terminal domain of BamC, comprised of two helix-grip motifs, is exposed on the surface of Escherichia coli. This unexpected topology of a bacterial lipoprotein is reminiscent of the analogous protein subunits from the mitochondrial β-barrel insertion machinery, the SAM complex. The modular arrangement and topological features provide new insight into the architecture of the BAM complex, towards a better understanding of the mechanism driving β-barrel membrane protein assembly.

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Section: Discussionmentioning

confidence: 90%

Dynamic Association of BAM Complex Modules Includes Surface Exposure of the Lipoprotein BamC

Webb

Selkrig

Perry

et al. 2012

Journal of Molecular Biology

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“…More recent bioinformatic approaches used to identify potential novel protein vaccine candidates against serogroup B N. meningitidis have identified several more lipoproteins (NMA1123, -1134, and -1091 [LolB] and NMB0033, -1163, -1946, and -2132 [sometimes NMB is replaced with GNA] [124,137]) that are immunogenic and generate bactericidal antibodies as determined by a serum bactericidal assay. The functions of many of these proteins are unknown, though LolB is recognized by the immune system and was initially identified through early immunological screens of meningococcal libraries with a monoclonal antibody, H.8, that had been developed to selectively recognize pathogenic neisserial strains (31,61).…”

Section: Biological Properties Of Lipoproteins Associated With Virulencementioning

confidence: 99%

Lipoproteins of Bacterial Pathogens

2011

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Lipid modification of bacterial proteins facilitates the anchoring of hydrophilic proteins to hydrophobic surfaces through the hydrophobic interaction of the attached acyl groups to the cell wall phospholipids. The addition of acyl moieties effectively provides a membrane anchor allowing the protein to function effectively in the aqueous environment (86). Bacterial lipoproteins have been shown to perform various roles, including nutrient uptake, signal transduction, adhesion, conjugation, and sporulation, and participate in antibiotic resistance, transport (such as ABC transporter systems), and extracytoplasmic folding of proteins (2,91,105,131,170). In

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“…During the last decade, the availability of meningococcal genome sequence data (Tettelin et al, 2000) has led to the identification of a number of less abundant (minor) cellsurface proteins with vaccine potential (Pajó n et al, 2009;Pizza et al, 2000). The FadL-like protein encoded by the NMB0088 ORF in the MC58 genome is an example and has been identified in meningococcal outer-membrane vesicles prepared from different strains (Uli et al, 2006;Vaughan et al, 2006;Vipond et al, 2006;Williams et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…This has implications for vaccine design: first, the sequence diversity of a meningococcal antigen provides evidence that it is indeed a target of the immune response and, second, it shows that a vaccine formulation containing as little as five protein variants has the potential to offer protection against the majority of hypervirulent lineages. An example of such a vaccine is the developmental NonaMen, which encompasses nine PorA protein types representing the major hypervirulent strains in circulation and should offer protection against the vast majority of invasive disease (van den Dobbelsteen et al, 2007).During the last decade, the availability of meningococcal genome sequence data (Tettelin et al, 2000) has led to the identification of a number of less abundant (minor) cellsurface proteins with vaccine potential (Pajó n et al, 2009;Pizza et al, 2000). The FadL-like protein encoded by the NMB0088 ORF in the MC58 genome is an example and has been identified in meningococcal outer-membrane vesicles prepared from different strains (Uli et al, 2006;Vaughan et al, 2006;Vipond et al, 2006;Williams et al, 2007).…”

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confidence: 99%

Variation in the Neisseria meningitidis FadL-like protein: an evolutionary model for a relatively low-abundance surface antigen

et al. 2010

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The molecular diversity of a novel Neisseria meningitidis antigen, encoded by the ORF NMB0088 of MC58 (FadL-like protein), was assessed in a panel of 64 diverse meningococcal strains. The panel consisted of strains belonging to different serogroups, serotypes, serosubtypes and MLST sequence types, of different clinical sources, years and countries of isolation. Based on the sequence variability of the protein, the FadL-like protein has been divided into four variant groups in this species. Antigen variants were associated with specific serogroups and MLST clonal complexes. Maximum-likelihood analyses were used to determine the relationships among sequences and to compare the selection pressures acting on the encoded protein. Furthermore, a model of population genetics and molecular evolution was used to detect natural selection in DNA sequences using the non-synonymous : synonymous substitution (d N : d S ) ratio. The meningococcal sequences were also compared with those of the related surface protein in non-pathogenic commensal Neisseria species to investigate potential horizontal gene transfer. The N. meningitidis fadL gene was subject to only weak positive selection pressure and was less diverse than meningococcal major outer-membrane proteins. The majority of the variability in fadL was due to recombination among existing alleles from the same or related species that resulted in a discrete mosaic structure in the meningococcal population. In general, the population structuring observed based on the FadL-like membrane protein indicates that it is under intermediate immune selection. However, the emergence of a new subvariant within the hyperinvasive lineages demonstrates the phenotypic adaptability of N. meningitidis, probably in response to selective pressure. INTRODUCTIONNeisseria meningitidis continues to be a major cause of meningitis and septicaemia worldwide, and meningococcal disease is one of the most aggressive bacterial infectious diseases in humans. Of the 13 distinct N. meningitidis serogroups only five are associated with invasive disease; of these, serogroups A, B and C account for approximately 90 % of all cases (Rosenstein et al., 2001). The disease continues to cause substantial morbidity and mortality in children worldwide despite the availability of effective antibiotics. Although early diagnosis and antibiotic treatment enhance survival, prevention through vaccination constitutes the most effective means to control meningococcal disease (Jó dar et al., 2002). Currently, there are successful glyconjugate vaccines against four (A, C, Y and W-135) of the five pathogenic serogroups (Mitka, 2005 as the basis of a vaccine for prevention of meningococcal diseases has been problematic, since the serogroup B capsular polysaccharide is identical to a widely distributed human carbohydrate, making it poorly immunogenic in humans and raising the possibility that it might elicit an auto-antibody response (Finne et al., 1987; Häyrinen et al., 1995). One potential vaccine strategy in the fight against me...

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Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes

Cited by 22 publications

References 71 publications

Dynamic Association of BAM Complex Modules Includes Surface Exposure of the Lipoprotein BamC

Dynamic Association of BAM Complex Modules Includes Surface Exposure of the Lipoprotein BamC

Lipoproteins of Bacterial Pathogens

Variation in the Neisseria meningitidis FadL-like protein: an evolutionary model for a relatively low-abundance surface antigen

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