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Full information on isolate FAM18 (id:698)

Projects

This isolate is a member of the following projects:

107 global collection
This dataset was originally used to validate MLST and was chosen to represent global diversity of N. meningitidis in the latter half of the Twentieth Century. It has been used in many publications since and the isolates are available as the EMGM MLST reference collection.
GMGL
Global Meningitis Genome Library: curated isolate data sets of N. meningtidis causing meningitis and/or septicaemia

Provenance/primary metadata

id
698
isolate
FAM18
aliases
BennettTree11; NIBSC_3076; Z4259
strain designation
C: P1.5,2: F1-30: ST-11 (cc11)
country
USA
continent
North America
year
1983
disease
invasive (unspecified/other)
epidemiology
endemic
species
Neisseria meningitidis
serogroup
C
genogroup
C
genogroup notes
C backbone: All essential capsule genes intact and present. Prediction code: https://github.com/ntopaz/characterize_neisseria_capsule.
capsule group
C
serotype
2a
sero subtype
P1.5,2
comments
Genome sequenced by the Sanger Institute

Tracking

sender
Mark Achtman, Max-Planck Institut fur Infektionsbiologie, Schumannstr. 21/22, Berlin, Germany
curator
Keith Jolley, University of Oxford, UK (E-mail: keith.jolley@zoo.ox.ac.uk)
update history
307 updates show details
date entered
2001-02-07
datestamp
2021-06-18

Secondary metadata

Vaccines

Bexsero reactivity
cross-reactive 
notes
Bexsero notes
NadA_peptide: 3 is cross-reactive to vaccine variant - data derived from MATS assays (PMID:23588089, PMID:26686998, PMID:26950303, PMID:27083425, PMID:29950334)
Trumenba reactivity
insufficient data 
notes

Bexsero® (4CMenB) is a multicomponent vaccine.

  • Protein-based meningococcal vaccines contain surface proteins as vaccine antigens, these proteins demonstrate nucleotide and amino acid sequence diversity.
  • Peptide sequence diversity can be analysed using the Bexsero Antigen Sequence Typing (BAST) scheme1.
  • Bexsero® contains: fHbp peptide 1; NHBA peptide 2; NadA peptide 8; PorA VR2 4.

The Deduced Vaccine Antigen Reactivity (MenDeVAR) Index was developed to combine multiple, complex data that inform the reactivity of each vaccine against specific antigenic variants.

The MenDeVAR Index:

  • isolate contains ≥1 exact sequence match to antigenic variants found in the vaccine.
  • isolate contains ≥1 antigenic variant deemed cross-reactive to vaccine variants through experimental studies.
  • all the isolate's antigenic variants have been deemed not cross-reactive to vaccine variants through experimental studies.
  • isolate contains antigens for which there is insufficient data from or are yet to be tested in experimental studies.

It is important to understand the caveats to interpreting the MenDeVAR Index:

Source of data - These data combine multiple sources of information including: peptide sequence identity through whole genome sequencing; experimental assays developed as indirect measures of the breadth of vaccine protection against diverse meningococci; and assays developed to assess immunogenicity. The Meningococcal Antigen Typing System (MATS)2 assay was used for Bexsero®.

Cross-reactivity definition - An antigenic variant was considered cross-reactive if it had been tested in ≥5 isolates/subjects and was above the accepted threshold in ≥75% of those isolates. This was established through combined analysis of published experimental studies (PMID provided for each variant), not from genomic data. These assays were based on serogroup B disease isolates.

Protein expression - We have not inferred from genomic data, therefore there may be isolates that possess genes but do no express the protein in vivo.

Age of vaccinees - For MATS assay development2, Bexsero® vaccine recipients were infants who had received 3 doses of vaccine and then a booster at 12 months. The pooled sera used for the MATS assay were taken from the toddlers at 13 months of age.

  1. Brehony C, Rodrigues CMC, Borrow R, et al. Distribution of Bexsero® Antigen Sequence Types (BASTs) in invasive meningococcal disease isolates: Implications for immunisation. Vaccine 2016 34(39):4690-7
  2. Donnelly J, Medini D, Boccadifuoco G, et al. Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines. Proc Natl Acad Sci USA 2010;107(45):19490-19495

MenDeVAR is described in Rodrigues et al. 2020, J Clin Microbiol 59(1):e02161-20. Please contact us if you have queries.

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Trumenba® (rLP2086) is a bivalent fHbp-containing vaccine.

  • Protein-based meningococcal vaccines contain surface proteins as vaccine antigens, these proteins demonstrate nucleotide and amino acid sequence diversity.
  • Peptide sequence diversity can be analysed using the fhbp peptide locus.
  • Trumenba® vaccine contains fHbp peptides 45 and 551.

The Deduced Vaccine Antigen Reactivity (MenDeVAR) Index was developed to combine multiple, complex data that inform the reactivity of each vaccine against specific antigenic variants.

The MenDeVAR Index:

  • isolate contains ≥1 exact sequence match to antigenic variants found in the vaccine.
  • isolate contains ≥1 antigenic variant deemed cross-reactive to vaccine variants through experimental studies.
  • all the isolate's antigenic variants have been deemed not cross-reactive to vaccine variants through experimental studies.
  • isolate contains antigens for which there is insufficient data from or are yet to be tested in experimental studies.

It is important to understand the caveats to interpreting the MenDeVAR Index:

Source of data - These data combine multiple sources of information including: peptide sequence identity through whole genome sequencing; experimental assays developed as indirect measures of the breadth of vaccine protection against diverse meningococci; and assays developed to assess immunogenicity. The meningococcal antigen surface expression (MEASURE)2 and serum bactericidal activity (SBA) assays were used for Trumenba®.

Cross-reactivity definition - An antigenic variant was considered cross-reactive if it had been tested in ≥5 isolates/subjects and was above the accepted threshold in ≥75% of those isolates. This was established through combined analysis of published experimental studies (PMID provided for each variant), not from genomic data. These assays were based on serogroup B disease isolates.

Age of vaccinees - The age of vaccine recipients in the experimental studies varies widely, ranging from toddlers to adults, and needs to be taken into consideration when interpreting results. Vaccine studies used different schedules and doses of vaccines.

  1. Jiang HQ, Hoiseth SK, Harris SL, et al. Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease. Vaccine 2010;28(37):6086-93
  2. McNeil LK, Donald RGK, Gribenko A, et al. Predicting the Susceptibility of Meningococcal Serogroup B Isolates to Bactericidal Antibodies Elicited by Bivalent rLP2086, a Novel Prophylactic Vaccine. mBio 2018;9(2):e00036-18

MenDeVAR is described in Rodrigues et al. 2020, J Clin Microbiol 59(1):e02161-20. Please contact us if you have queries.

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Publications (15)

  • Bennett JS, Bentley SD, Vernikos GS, Quail MA, Cherevach I, White B, Parkhill J, Maiden MC (2010). Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06. BMC Genomics 11:652
  • Bennett JS, Jolley KA, Earle SG, Corton C, Bentley SD, Parkhill J, Maiden MC (2012). A genomic approach to bacterial taxonomy: an examination and proposed reclassification of species within the genus Neisseria. Microbiology 158:1570-80
  • Bennett JS, Jolley KA, Maiden MC (2013). Genome sequence analyses show that Neisseria oralis is the same species as 'Neisseria mucosa var. heidelbergensis'. Int J Syst Evol Microbiol 63:3920-6
  • Bentley SD, Vernikos GS, Snyder LA, Churcher C, Arrowsmith C, Chillingworth T, Cronin A, Davis PH, Holroyd NE, Jagels K, Maddison M, Moule S, Rabbinowitsch E, Sharp S, Unwin L, Whitehead S, Quail MA, Achtman M, Barrell B, Saunders NJ, Parkhill J (2007). Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18. PLoS Genet 3:e23
  • Bratcher HB, Corton C, Jolley KA, Parkhill J, Maiden MC (2014). A gene-by-gene population genomics platform: de novo assembly, annotation and genealogical analysis of 108 representative Neisseria meningitidis genomes. BMC Genomics 15:1138
  • Brik A, Terrade A, Hong E, Deghmane A, Taha MK, Bouafsoun A, Khmiri M, Boussetta K, Boukhir S, Jaballah NB, Kechrid A, Smaoui H (2020). Phenotypic and genotypic characterization of meningococcal isolates in Tunis, Tunisia: High diversity and impact on vaccination strategies. Int J Infect Dis 91:73-78
  • Budroni S, Siena E, Dunning Hotopp JC, Seib KL, Serruto D, Nofroni C, Comanducci M, Riley DR, Daugherty SC, Angiuoli SV, Covacci A, Pizza M, Rappuoli R, Moxon ER, Tettelin H, Medini D (2011). Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination. Proc Natl Acad Sci U S A 108:4494-9
  • Diallo K, MacLennan J, Harrison OB, Msefula C, Sow SO, Daugla DM, Johnson E, Trotter C, MacLennan CA, Parkhill J, Borrow R, Greenwood BM, Maiden MCJ (2019). Genomic characterization of novel Neisseria species. Sci Rep 9:13742
  • Feavers IM, Gray SJ, Urwin R, Russell JE, Bygraves JA, Kaczmarski EB, Maiden MC (1999). Multilocus sequence typing and antigen gene sequencing in the investigation of a meningococcal disease outbreak. J Clin Microbiol 37:3883-7
  • Jolley KA, Hill DM, Bratcher HB, Harrison OB, Feavers IM, Parkhill J, Maiden MC (2012). Resolution of a meningococcal disease outbreak from whole-genome sequence data with rapid Web-based analysis methods. J Clin Microbiol 50:3046-53
  • Katz LS, Sharma NV, Harcourt BH, Thomas JD, Wang X, Mayer LW, Jordan IK (2011). Using single-nucleotide polymorphisms to discriminate disease-associated from carried genomes of Neisseria meningitidis. J Bacteriol 193:3633-41
  • Klughammer J, Dittrich M, Blom J, Mitesser V, Vogel U, Frosch M, Goesmann A, Müller T, Schoen C (2017). Comparative Genome Sequencing Reveals Within-Host Genetic Changes in Neisseria meningitidis during Invasive Disease. PLoS One 12:e0169892
  • Lucidarme J, Hill DM, Bratcher HB, Gray SJ, du Plessis M, Tsang RS, Vazquez JA, Taha MK, Ceyhan M, Efron AM, Gorla MC, Findlow J, Jolley KA, Maiden MC, Borrow R (2015). Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage. J Infect 71:544-52
  • Lucidarme J, Lekshmi A, Parikh SR, Bray JE, Hill DM, Bratcher HB, Gray SJ, Carr AD, Jolley KA, Findlow J, Campbell H, Ladhani SN, Ramsay ME, Maiden MCJ, Borrow R (2017). Frequent capsule switching in 'ultra-virulent' meningococci - Are we ready for a serogroup B ST-11 complex outbreak? J Infect 75:95-103
  • Stabler RA, Marsden GL, Witney AA, Li Y, Bentley SD, Tang CM, Hinds J (2005). Identification of pathogen-specific genes through microarray analysis of pathogenic and commensal Neisseria species. Microbiology 151:2907-22

Sequence bin

contigs
1
length
2,194,961 bp
%GC
51.62
Ns
0
gaps
0
loci tagged
2,233

Show sequence bin

Annotation quality metrics

SchemeScheme lociDesignated lociAnnotation
ScoreStatus
rplF species11100
Finetyping antigens33100
Bexsero Antigen Sequence Typing (BAST)55100
MLST77100
Ribosomal MLST5353100
N. meningitidis cgMLST v1.01605160399

Analysis

rMLST species identification

RankTaxonTaxonomySupportMatches
SPECIES Neisseria meningitidis Proteobacteria > Betaproteobacteria > Neisseriales > Neisseriaceae > Neisseria > Neisseria meningitidis 100%

Analysis performed: 2021-03-30

Similar isolates (determined by classification schemes)

Experimental schemes are subject to change and are not a stable part of the nomenclature.

Classification schemeUnderlying schemeClustering methodMismatch thresholdStatusGroup
Bact_rmlstc_20Ribosomal MLSTSingle-linkage20experimental169 (24212 isolates)
Bact_rmlstc_10Ribosomal MLSTSingle-linkage10experimental475 (6052 isolates)
Bact_rmlstc_5Ribosomal MLSTSingle-linkage5experimental696 (4358 isolates)
Bact_rmlstc_4Ribosomal MLSTSingle-linkage4experimental796 (4351 isolates)
Bact_rmlstc_3Ribosomal MLSTSingle-linkage3experimental917 (4332 isolates)
Bact_rmlstc_2Ribosomal MLSTSingle-linkage2experimental1121 (4204 isolates)
Bact_rmlstc_1Ribosomal MLSTSingle-linkage1experimental1599 (4117 isolates)
Nm_cgc_200N. meningitidis cgMLST v1.0Single-linkage200experimental65 (3870 isolates)
Nm_cgc_100N. meningitidis cgMLST v1.0Single-linkage100experimental42 (3 isolates)
Nm_cgc_50N. meningitidis cgMLST v1.0Single-linkage50experimental50 (3 isolates)
Nm_cgc_25N. meningitidis cgMLST v1.0Single-linkage25experimental50 (3 isolates)
Bact_rmlstc_20Ribosomal MLSTSingle-linkage20experimental169 (24212 isolates)
Bact_rmlstc_10Ribosomal MLSTSingle-linkage10experimental475 (6052 isolates)
Bact_rmlstc_5Ribosomal MLSTSingle-linkage5experimental696 (4358 isolates)
Bact_rmlstc_4Ribosomal MLSTSingle-linkage4experimental796 (4351 isolates)
Bact_rmlstc_3Ribosomal MLSTSingle-linkage3experimental917 (4332 isolates)
Bact_rmlstc_2Ribosomal MLSTSingle-linkage2experimental1121 (4204 isolates)
Bact_rmlstc_1Ribosomal MLSTSingle-linkage1experimental1599 (4117 isolates)
Nm_cgc_200N. meningitidis cgMLST v1.0Single-linkage200experimental65 (3870 isolates)
Nm_cgc_100N. meningitidis cgMLST v1.0Single-linkage100experimental42 (3 isolates)
Nm_cgc_50N. meningitidis cgMLST v1.0Single-linkage50experimental50 (3 isolates)
Nm_cgc_25N. meningitidis cgMLST v1.0Single-linkage25experimental50 (3 isolates)

Schemes and loci

Navigate and select schemes within tree to display allele designations

Tools

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