Dataset Information

Evolution of an outbreak of meningococcal disease among men who have sex with men

ABSTRACT: Neisseria meningitidis (meningococcus) is usually transmitted via respiratory droplets, whereas its close relative, the gonococcus is sexually transmitted. Invasive meningococcal disease due to isolates of serogroup C increased in Europe and the United States among men who have sex with men (MSM). These isolates were also recovered from cases of urethritis suggesting sexual transmission. Genome sequencing of representative strains revealed that isolates from MSM and urethritis cases belonged to a unique clade within clonal complex11. Proteome analysis showed expression of nitrite reductase by these isolates, enabling anaerobic growth as in gonococci. Invasive isolates from MSM, but not urethritis isolates expressed functional human factor H (hfH) binding protein associated with enhanced survival in transgenic mice expressing hfH, a complement regulatory protein. Our data provide a unique example of meningococcal evolution with adaptation to sexual transmissibility, initially associated with low virulence but with subsequent fHbp-associated invasiveness. Implications for vaccination strategies are discussed.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Neisseria Meningitidis Serogroup C / Serotype 2a (strain Atcc 700532 / Dsm 15464 / Fam18)

SUBMITTER: Andreas Otto

LAB HEAD: Andreas Otto

PROVIDER: PXD001498 | Pride | 2016-05-18

REPOSITORIES: Pride

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Publications

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men.

Taha Muhamed-Kheir MK Claus Heike H Lappann Martin M Veyrier Frédéric J FJ Otto Andreas A Becher Dörte D Deghmane Ala-Eddine AE Frosch Matthias M Hellenbrand Wiebke W Hong Eva E Parent du Châtelet Isabelle I Prior Karola K Harmsen Dag D Vogel Ulrich U

PloS one 20160511 5

Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isola ...[more]

PMID: 27167067

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Project description:Vaccines to prevent capsular group B meningococcal disease have been based on proteins, as the polysaccharide capsule was deemed unsuitable due to its similarity to human tissues. Outer membrane vesicle (OMV) vaccines have been targeted at specific capsular group B epidemics in Cuba, Norway, and New Zealand, with the major immunogen determined as porin A (PorA). Subcapsular protein vaccines aim to increase breadth of coverage of meningococcal strains, by the inclusion of protein variants from many different clonal complexes (ccs). Using scalable and portable genomic techniques, it is possible to study the diversity of OMV and subcapsular proteins in relevant meningococcal populations. Shotgun proteomics identified 461 proteins in the OMVs derived from NZ98/254, a component of the Bexsero® vaccine, with a complex proteome comprised of outer membrane proteins and proteins from other cellular compartments. Amino acid sequences for 24 selected proteins were catalogued within the PubMLST Neisseria database as part of the OMV peptide Typing (OMVT) scheme. Of the 24 proteins included, there was variation in the extent of diversity and association with ccs from the most conserved peptides FbpA (NEISp0578) and putative periplasmic proteins (NEISp1063) to the most diverse TbpA (NEISp1690). There were 1752 OMVTs identified amongst 2492/3506 isolates. OMVTs were further grouped into clusters (identical at ≥18 peptide sequences), 45.3% of isolates were assigned to one of 27 OMVT clusters. Both OMVTs and clusters were strongly associated with cc, genogroup and recombinant Bexsero® antigens. The OMVT scheme represents an open-access, web-based tool for the systematic analysis of the multiple components of OMV vaccines, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with both genogroup and Bexsero® Antigen Sequence type (BAST). This highly structured population of disease-causing meningococci is consistent with proposed effects of host immune selection and competition between allelic variants on meningococcal population structure. This has implications for future vaccine assessment, and development, especially the choice of antigen combinations. The methodology is portable and will facilitate region-specific WGS interrogation, allowing informed choices about vaccine development or implementation.

Dataset Information

Evolution of an outbreak of meningococcal disease among men who have sex with men

Publications

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men.

Similar Datasets

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