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  1. Article ; Online: Pooled-sera hSBA titres predict individual seroprotection in infants and toddlers vaccinated with 4CMenB.

    Budroni, Sonia / Kleinschmidt, Annett / Boucher, Philip / Medini, Duccio

    Vaccine

    2016  Volume 34, Issue 23, Page(s) 2579–2584

    Abstract: Unlabelled: The Serum Bactericidal Antibody assay with human complement (hSBA) using individual immune sera is a surrogate of protection for meningococcal vaccines. Strain coverage of 4CMenB, a licensed vaccine against serogroup B meningococcal (MenB) ... ...

    Abstract Unlabelled: The Serum Bactericidal Antibody assay with human complement (hSBA) using individual immune sera is a surrogate of protection for meningococcal vaccines. Strain coverage of 4CMenB, a licensed vaccine against serogroup B meningococcal (MenB) disease, has been extensively assessed in hSBA using pooled sera, directly or through the Meningococcal Antigen Typing System (MATS). The extent to which pooled-sera hSBA titres reflect individual protection is not yet fully understood. We analysed more than 17000 individual hSBA titres from infants and toddlers vaccinated with 4CMenB, pooled-serum hSBA titres from subsets therein and MATS data from a 40 strain panel representative of invasive MenB disease in England and Wales. Individual hSBA titres segregated in two normal distributions, respectively from responding and non-responding subjects (fit_model-data: r=0.996, p-values <0.05). No individual subject showed abnormally high titres compared to the distributions. Also, when sera from the same subjects were tested individually and in pool, pooled-sera titre and average of individual titres from the same group were substantially indistinguishable (r=0.97, p-value <<0.001). We identified a robust mathematical relationship between the mean of individual hSBA titres and the proportion of subjects achieving a protective titre (seroprotection rate, r=0.95, p-value <<0.001). Using this relation, the seroprotection rate in 15 groups of vaccinees tested against 11 diverse meningococcal isolates was accurately predicted by the hSBA titre of the respective pooled sera (average prediction error 9%). Finally, strains defined covered by MATS had on average 77% predicted seroprotection rate (interquartile range, IQR: 66-100%) and 39% for non-covered strains (IQR: 19-46%). We conclude that seroprotection rates in infants and toddlers vaccinated with 4CMenB can be accurately predicted by pooled-serum hSBA, and that strain coverage defined by MATS is associated with high seroprotection rates.
    Summary: The Serum Bactericidal Antibody assay (SBA) from individual sera is a surrogate of protection for meningococcal vaccines. We show that SBA performed on pooled sera predicts individual protection.
    MeSH term(s) Antibodies, Bacterial/blood ; Antigens, Bacterial/immunology ; England ; Humans ; Infant ; Meningococcal Infections/prevention & control ; Meningococcal Vaccines/therapeutic use ; Models, Theoretical ; Neisseria meningitidis, Serogroup B ; Predictive Value of Tests ; Randomized Controlled Trials as Topic ; Serum Bactericidal Antibody Assay ; Wales
    Chemical Substances 4CMenB vaccine ; Antibodies, Bacterial ; Antigens, Bacterial ; Meningococcal Vaccines
    Language English
    Publishing date 2016-05-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2016.04.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Pooled-sera hSBA titres predict individual seroprotection in infants and toddlers vaccinated with 4CMenB

    Budroni, Sonia / Annett Kleinschmidt / Duccio Medini / Philip Boucher

    Vaccine. 2016 May 17, v. 34, no. 23

    2016  

    Abstract: The Serum Bactericidal Antibody assay with human complement (hSBA) using individual immune sera is a surrogate of protection for meningococcal vaccines. Strain coverage of 4CMenB, a licensed vaccine against serogroup B meningococcal (MenB) disease, has ... ...

    Abstract The Serum Bactericidal Antibody assay with human complement (hSBA) using individual immune sera is a surrogate of protection for meningococcal vaccines. Strain coverage of 4CMenB, a licensed vaccine against serogroup B meningococcal (MenB) disease, has been extensively assessed in hSBA using pooled sera, directly or through the Meningococcal Antigen Typing System (MATS). The extent to which pooled-sera hSBA titres reflect individual protection is not yet fully understood.We analysed more than 17000 individual hSBA titres from infants and toddlers vaccinated with 4CMenB, pooled-serum hSBA titres from subsets therein and MATS data from a 40 strain panel representative of invasive MenB disease in England and Wales.Individual hSBA titres segregated in two normal distributions, respectively from responding and non-responding subjects (fit_model-data: r=0.996, p-values <0.05). No individual subject showed abnormally high titres compared to the distributions. Also, when sera from the same subjects were tested individually and in pool, pooled-sera titre and average of individual titres from the same group were substantially indistinguishable (r=0.97, p-value <<0.001).We identified a robust mathematical relationship between the mean of individual hSBA titres and the proportion of subjects achieving a protective titre (seroprotection rate, r=0.95, p-value <<0.001). Using this relation, the seroprotection rate in 15 groups of vaccinees tested against 11 diverse meningococcal isolates was accurately predicted by the hSBA titre of the respective pooled sera (average prediction error 9%).Finally, strains defined covered by MATS had on average 77% predicted seroprotection rate (interquartile range, IQR: 66–100%) and 39% for non-covered strains (IQR: 19–46%).We conclude that seroprotection rates in infants and toddlers vaccinated with 4CMenB can be accurately predicted by pooled-serum hSBA, and that strain coverage defined by MATS is associated with high seroprotection rates.The Serum Bactericidal Antibody assay (SBA) from individual sera is a surrogate of protection for meningococcal vaccines. We show that SBA performed on pooled sera predicts individual protection.
    Keywords antibodies ; antigens ; antiserum ; blood serum ; complement ; humans ; infants ; prediction ; serotypes ; toddlers ; vaccines ; England
    Language English
    Dates of publication 2016-0517
    Size p. 2579-2584.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2016.04.009
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: Computational modeling of microfluidic data provides high-throughput affinity estimates for monoclonal antibodies

    Budroni, Sonia / Buricchi, Francesca / Cavallone, Andrea / Volpini, Gianfranco / Mariani, Alessandra / Lo Surdo, Paola / Blohmke, Christoph J. / Del Giudice, Giuseppe / Medini, Duccio / Finco, Oretta

    Computational and Structural Biotechnology Journal. 2021, v. 19

    2021  

    Abstract: Affinity measurement is a fundamental step in the discovery of monoclonal antibodies (mAbs) and of antigens suitable for vaccine development. Innovative affinity assays are needed due to the low throughput and/or limited dynamic range of available ... ...

    Abstract Affinity measurement is a fundamental step in the discovery of monoclonal antibodies (mAbs) and of antigens suitable for vaccine development. Innovative affinity assays are needed due to the low throughput and/or limited dynamic range of available technologies.We combined microfluidic technology with quantum-mechanical scattering theory, in order to develop a high-throughput, broad-range methodology to measure affinity. Fluorescence intensity profiles were generated for out-of-equilibrium solutions of labelled mAbs and their antigen-binding fragments migrating along micro-columns with immobilized cognate antigen. Affinity quantification was performed by computational data analysis based on the Landau probability distribution.Experiments using a wide array of human or murine antibodies against bacterial or viral, protein or polysaccharide antigens, showed that all the antibody-antigen capture profiles (n = 841) generated at different concentrations were accurately described by the Landau distribution.A scale parameter W, proportional to the full-width-at-half-maximum of the capture profile, was shown to be independent of the antibody concentration. The W parameter correlated significantly (Pearson’s r [p–value]: 0.89 [3 × 10⁻⁸]) with the equilibrium dissociation constant KD, a gold-standard affinity measure.Our method showed good intermediate precision (median coefficient of variation: 5%) and a dynamic range corresponding to KD values spanning from ~10⁻⁷ to ~10⁻¹¹ Molar. Relative to assays relying on antibody-antigen equilibrium in solution, even when they are microfluidic-based, the method’s turnaround times were decreased from 2 days to 2 h.The described computational modelling of antibody capture profiles represents a fast, reproducible, high-throughput methodology to accurately measure a broad range of antibody affinities in very low volumes of solution.
    Keywords antigens ; biotechnology ; dissociation ; fluorescence ; humans ; mice ; microfluidic technology ; polysaccharides ; probability ; vaccine development
    Language English
    Size p. 3664-3672.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2694435-2
    ISSN 2001-0370
    ISSN 2001-0370
    DOI 10.1016/j.csbj.2021.06.024
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Computational modeling of microfluidic data provides high-throughput affinity estimates for monoclonal antibodies.

    Budroni, Sonia / Buricchi, Francesca / Cavallone, Andrea / Volpini, Gianfranco / Mariani, Alessandra / Lo Surdo, Paola / Blohmke, Christoph J / Del Giudice, Giuseppe / Medini, Duccio / Finco, Oretta

    Computational and structural biotechnology journal

    2021  Volume 19, Page(s) 3664–3672

    Abstract: Affinity measurement is a fundamental step in the discovery of monoclonal antibodies (mAbs) and of antigens suitable for vaccine development. Innovative affinity assays are needed due to the low throughput and/or limited dynamic range of available ... ...

    Abstract Affinity measurement is a fundamental step in the discovery of monoclonal antibodies (mAbs) and of antigens suitable for vaccine development. Innovative affinity assays are needed due to the low throughput and/or limited dynamic range of available technologies. We combined microfluidic technology with quantum-mechanical scattering theory, in order to develop a high-throughput, broad-range methodology to measure affinity. Fluorescence intensity profiles were generated for out-of-equilibrium solutions of labelled mAbs and their antigen-binding fragments migrating along micro-columns with immobilized cognate antigen. Affinity quantification was performed by computational data analysis based on the Landau probability distribution. Experiments using a wide array of human or murine antibodies against bacterial or viral, protein or polysaccharide antigens, showed that all the antibody-antigen capture profiles (n = 841) generated at different concentrations were accurately described by the Landau distribution. A scale parameter
    Language English
    Publishing date 2021-06-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2694435-2
    ISSN 2001-0370
    ISSN 2001-0370
    DOI 10.1016/j.csbj.2021.06.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Dissecting the Human Response to

    Leuzzi, Rosanna / Bodini, Margherita / Thomsen, Isaac P / Soldaini, Elisabetta / Bartolini, Erika / Muzzi, Alessandro / Clemente, Bruna / Galletti, Bruno / Manetti, Andrea Guido Oreste / Giovani, Cinzia / Censini, Stefano / Budroni, Sonia / Spensieri, Fabiana / Borgogni, Erica / Rossi Paccani, Silvia / Margarit, Immaculada / Bagnoli, Fabio / Giudice, Giuseppe Del / Creech, Clarence B

    Frontiers in immunology

    2021  Volume 12, Page(s) 749432

    Abstract: Staphylococcus ... ...

    Abstract Staphylococcus aureus
    MeSH term(s) Adult ; Antibodies, Bacterial/blood ; Antigens, Bacterial/immunology ; Child ; Cytokines/blood ; Humans ; Immunoglobulin G/blood ; Protein Array Analysis ; Staphylococcal Infections/blood ; Staphylococcal Infections/genetics ; Staphylococcal Infections/immunology ; Staphylococcus aureus/immunology ; Virulence Factors/immunology
    Chemical Substances Antibodies, Bacterial ; Antigens, Bacterial ; Cytokines ; Immunoglobulin G ; Virulence Factors
    Language English
    Publishing date 2021-11-08
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.749432
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: 4CMenB Immunization Induces Serum Bactericidal Antibodies Against Non-Serogroup B Meningococcal Strains in Adolescents.

    Biolchi, Alessia / Tomei, Sara / Brunelli, Brunella / Giuliani, Maria / Bambini, Stefania / Borrow, Ray / Claus, Heike / Gorla, Maria Cecilia O / Hong, Eva / Lemos, Ana Paula S / Lucidarme, Jay / Taha, Muhamed-Kheir / Vogel, Ulrich / Budroni, Sonia / Giuliani, Marzia M / Rappuoli, Rino / Boucher, Philip / Pizza, Mariagrazia

    Infectious diseases and therapy

    2020  Volume 10, Issue 1, Page(s) 307–316

    Abstract: Introduction: Invasive meningococcal disease (IMD) is an important public health concern. In developed countries, most IMD is caused by meningococcal serogroup B (MenB) and two protein-based MenB vaccines are currently available: the four-component ... ...

    Abstract Introduction: Invasive meningococcal disease (IMD) is an important public health concern. In developed countries, most IMD is caused by meningococcal serogroup B (MenB) and two protein-based MenB vaccines are currently available: the four-component vaccine 4CMenB (Bexsero, GSK) and the bivalent vaccine MenB-FHbp (Trumenba, Pfizer). Genes encoding the 4CMenB vaccine antigens are also present in strains belonging to other meningococcal serogroups.
    Methods: To evaluate the potential of 4CMenB vaccination to protect adolescents against non-MenB IMD, we tested the bactericidal activity of sera from immunized adolescents on 147 (127 European and 20 Brazilian) non-MenB IMD isolates, with a serum bactericidal antibody assay using human complement (hSBA). Serum pools were prepared using samples from randomly selected participants in various clinical trials, pre- and post-vaccination: 12 adolescents who received two doses of 4CMenB 2 months apart, and 10 adolescents who received a single dose of a MenACWY conjugate vaccine (as positive control).
    Results: 4CMenB pre-immune sera killed 7.5% of the 147 non-MenB isolates at hSBA titers ≥ 1:4. In total, 91 (61.9%) tested isolates were killed by post-dose 2 pooled sera at hSBA titers ≥ 1:4, corresponding to 44/80 (55.0%) MenC, 26/35 (74.3%) MenW, and 21/32 (65.6%) MenY isolates killed.
    Conclusion: 4CMenB vaccination in adolescents induces bactericidal killing of non-MenB isolates, suggesting that mass vaccination could impact IMD due to serogroups other than MenB.
    Language English
    Publishing date 2020-11-13
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2701611-0
    ISSN 2193-6382 ; 2193-8229
    ISSN (online) 2193-6382
    ISSN 2193-8229
    DOI 10.1007/s40121-020-00370-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Antibody avidity, persistence, and response to antigen recall: comparison of vaccine adjuvants.

    Budroni, Sonia / Buricchi, Francesca / Cavallone, Andrea / Bourguignon, Patricia / Caubet, Magalie / Dewar, Vincent / D'Oro, Ugo / Finco, Oretta / Garçon, Nathalie / El Idrissi, Mohamed / Janssens, Michel / Leroux-Roels, Geert / Marchant, Arnaud / Schwarz, Tino / Van Damme, Pierre / Volpini, Gianfranco / van der Most, Robbert / Didierlaurent, Arnaud M / Burny, Wivine

    NPJ vaccines

    2021  Volume 6, Issue 1, Page(s) 78

    Abstract: Differences in innate immune 'imprinting' between vaccine adjuvants may mediate dissimilar effects on the quantity/quality of persisting adaptive responses. We compared antibody avidity maturation, antibody/memory B cell/ ... ...

    Abstract Differences in innate immune 'imprinting' between vaccine adjuvants may mediate dissimilar effects on the quantity/quality of persisting adaptive responses. We compared antibody avidity maturation, antibody/memory B cell/CD4
    Language English
    Publishing date 2021-05-21
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-021-00337-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Multicomponent meningococcal serogroup B vaccination elicits cross-reactive immunity in infants against genetically diverse serogroup C, W and Y invasive disease isolates.

    Biolchi, Alessia / De Angelis, Gabriella / Moschioni, Monica / Tomei, Sara / Brunelli, Brunella / Giuliani, Maria / Bambini, Stefania / Borrow, Ray / Claus, Heike / Gorla, Maria Cecilia O / Hong, Eva / Lemos, Ana Paula S / Lucidarme, Jay / Taha, Muhamed-Kheir / Vogel, Ulrich / Comanducci, Maurizio / Budroni, Sonia / Giuliani, Marzia M / Rappuoli, Rino /
    Pizza, Mariagrazia / Boucher, Philip

    Vaccine

    2020  Volume 38, Issue 47, Page(s) 7542–7550

    Abstract: Background: The multicomponent meningococcal serogroup B vaccine (4CMenB) is currently indicated for active immunization against invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB). However, genes encoding the 4CMenB ... ...

    Abstract Background: The multicomponent meningococcal serogroup B vaccine (4CMenB) is currently indicated for active immunization against invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB). However, genes encoding the 4CMenB antigens are also variably present and expressed in strains belonging to other meningococcal serogroups. In this study, we evaluated the ability of antibodies raised by 4CMenB immunisation to induce complement-mediated bactericidal killing of non-MenB strains.
    Methods: A total of 227 invasive non-MenB disease isolates were collected between 1 July 2007 and 30 June 2008 from England and Wales, France, and Germany; 41 isolates were collected during 2012 from Brazil. The isolates were subjected to genotypic analyses. A subset of 147 isolates (MenC, MenW and MenY) representative of the meningococcal genetic diversity of the total sample were tested in the human complement serum bactericidal antibody assay (hSBA) using sera from infants immunised with 4CMenB.
    Results: Serogroup and clonal complex repertoires of non-MenB isolates were different for each country. For the European panel, MenC, MenW and MenY isolates belonged mainly to ST-11, ST-22 and ST-23 complexes, respectively. For the Brazilian panel, most MenC and MenW isolates belonged to the ST-103 and ST-11 complexes, respectively, and most MenY isolates were not assigned to clonal complexes. Of the 147 non-MenB isolates, 109 were killed in hSBA, resulting in an overall coverage of 74%.
    Conclusion: This is the first study in which 147 non-MenB serogroup isolates have been analysed in hSBA to evaluate the potential of a MenB vaccine to cover strains belonging to other serogroups. These data demonstrate that antibodies raised by 4CMenB are able to induce bactericidal killing of 109 non-MenB isolates, representative of non-MenB genetic and geographic diversity. These findings support previous evidence that 4CMenB immunisation can provide cross-protection against non-MenB strains in infants, which represents an added benefit of 4CMenB vaccination.
    MeSH term(s) Antigens, Bacterial/genetics ; Brazil ; England ; France ; Germany ; Humans ; Infant ; Meningococcal Infections/prevention & control ; Meningococcal Vaccines ; Neisseria meningitidis, Serogroup B/genetics ; Serogroup ; Vaccination ; Wales
    Chemical Substances Antigens, Bacterial ; Meningococcal Vaccines
    Language English
    Publishing date 2020-10-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2020.09.050
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  9. Article ; Online: Building an insurance against modern pandemics.

    Rappuoli, Rino / Medini, Duccio / Siena, Emilio / Budroni, Sonia / Dormitzer, Philip R / Del Giudice, Giuseppe

    Current opinion in investigational drugs (London, England : 2000)

    2010  Volume 11, Issue 2, Page(s) 126–130

    Abstract: The response to the first influenza pandemic of the 21st century benefited from the extensive preparation for an avian influenza pandemic and the mild nature of the 2009 A/H1N1 swine influenza virus. However, the pandemic demonstrated the limited ability ...

    Abstract The response to the first influenza pandemic of the 21st century benefited from the extensive preparation for an avian influenza pandemic and the mild nature of the 2009 A/H1N1 swine influenza virus. However, the pandemic demonstrated the limited ability to predict influenza pandemics, to anticipate levels of cross-protection, and to deliver vaccines in a timely manner, particularly to low income countries. The lessons learned from the 2009 H1N1 pandemic are of paramount importance to develop more effective preparations against future pandemics.
    MeSH term(s) Developing Countries ; Disease Outbreaks/prevention & control ; Humans ; Influenza A Virus, H1N1 Subtype/isolation & purification ; Influenza A virus/isolation & purification ; Influenza Vaccines/administration & dosage ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Influenza, Human/transmission
    Chemical Substances Influenza Vaccines
    Language English
    Publishing date 2010-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2027913-9
    ISSN 2040-3429 ; 0967-8298 ; 1472-4472
    ISSN (online) 2040-3429
    ISSN 0967-8298 ; 1472-4472
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  10. Article ; Online: Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination.

    Budroni, Sonia / Siena, Emilio / Dunning Hotopp, Julie C / Seib, Kate L / Serruto, Davide / Nofroni, Chiara / Comanducci, Maurizio / Riley, David R / Daugherty, Sean C / Angiuoli, Samuel V / Covacci, Antonello / Pizza, Mariagrazia / Rappuoli, Rino / Moxon, E Richard / Tettelin, Hervé / Medini, Duccio

    Proceedings of the National Academy of Sciences of the United States of America

    2011  Volume 108, Issue 11, Page(s) 4494–4499

    Abstract: Molecular data on a limited number of chromosomal loci have shown that the population of Neisseria meningitidis (Nm), a deadly human pathogen, is structured in distinct lineages. Given that the Nm population undergoes substantial recombination, the ... ...

    Abstract Molecular data on a limited number of chromosomal loci have shown that the population of Neisseria meningitidis (Nm), a deadly human pathogen, is structured in distinct lineages. Given that the Nm population undergoes substantial recombination, the mechanisms resulting in the evolution of these lineages, their persistence in time, and the implications for the pathogenicity of the bacterium are not yet completely understood. Based on whole-genome sequencing, we show that Nm is structured in phylogenetic clades. Through acquisition of specific genes and through insertions and rearrangements, each clade has acquired and remodeled specific genomic tracts, with the potential to impact on the commensal and virulence behavior of Nm. Despite this clear evidence of a structured population, we confirm high rates of detectable recombination throughout the whole Nm chromosome. However, gene conversion events were found to be longer within clades than between clades, suggesting a DNA cleavage mechanism associated with the phylogeny of the species. We identify 22 restriction modification systems, probably acquired by horizontal gene transfer from outside of the species/genus, whose distribution in the different strains coincides with the phylogenetic clade structure. We provide evidence that these clade-associated restriction modification systems generate a differential barrier to DNA exchange consistent with the observed population structure. These findings have general implications for the emergence of lineage structure and virulence in recombining bacterial populations, and they could provide an evolutionary framework for the population biology of a number of other bacterial species that show contradictory population structure and dynamics.
    MeSH term(s) Base Sequence ; Chromosome Inversion/genetics ; Chromosome Segregation/genetics ; Conserved Sequence/genetics ; DNA Restriction-Modification Enzymes/genetics ; DNA, Bacterial/genetics ; Gene Conversion/genetics ; Genes, Bacterial/genetics ; Host-Pathogen Interactions/genetics ; Humans ; Mutagenesis, Insertional/genetics ; Neisseria meningitidis/classification ; Neisseria meningitidis/genetics ; Neisseria meningitidis/growth & development ; Neisseria meningitidis/pathogenicity ; Operon/genetics ; Phylogeny ; Recombination, Genetic ; Species Specificity
    Chemical Substances DNA Restriction-Modification Enzymes ; DNA, Bacterial
    Language English
    Publishing date 2011-02-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1019751108
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