ArticleNature communications2019
Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 3 pooled it
9.3field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 3 syntheses or guidelines pooled it, 117 citations in OpenAlex.
- Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.International journal of molecular sciences · 2023Pooled it
- Pooled it
- Analysing pneumococcal invasiveness using Bayesian models of pathogen progression rates.PLoS computational biology · 2022Pooled it
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- Capsular specificity in temperate phages of Klebsiella pneumoniae is driven by diverse receptor-binding enzymes.PLoS biology · 2026Article
- Brain Abscesses Complicating Bacterial Meningitis-A Nationwide Cohort Study From the Netherlands.European journal of neurology · 2026Article
- Genomic variants distinguish Pseudomonas aeruginosa from cystic fibrosis sputum and bloodstream infection.BMC infectious diseases · 2026Article
- mTORC1 inhibition by sirolimus as adjunctive treatment in experimental pneumococcal meningitis.Brain communications · 2026Article
- Article
- Identification of predictors for bacterial meningitis diagnosis based on transcriptomics and genetic analysis.AMB Express · 2025Article
- Article
- Inference of Host-Pathogen Interaction Matrices from Genome-Wide Polymorphism Data.Molecular biology and evolution · 2024Article
- Toward Ecologically Relevant Genetics of Interactions Between Host Plants and Plant Growth-Promoting Bacteria.Advanced genetics (Hoboken, N.J.) · 2024Article
- Otitis in Patients With Community-Acquired Bacterial Meningitis: A Nationwide Prospective Cohort Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- Article
- Biological puzzles solved by usingJournal of bacteriology · 2024Review
- Detecting co-selection through excess linkage disequilibrium in bacterial genomes.NAR genomics and bioinformatics · 2024Article
- Article
- Long-term evolution of Streptococcus mitis and Streptococcus pneumoniae leads to higher genetic diversity within rather than between human populations.PLoS genetics · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
40 authors at 18 institutions in 5 countries.
John A LeesDepartment of Microbiology, New York University School of Medicine, New York, NY, 10016, USA.ORCID http://orcid.org/0000-0001-5360-1254
Bart FerwerdaAmsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.ORCID http://orcid.org/0000-0002-7050-5931
Philip H C KremerAmsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
Nicole E WheelerParasites and Microbes, Wellcome Sanger Institute, Cambridge, CB10 1SA, UK.
Mercedes Valls SerónAmsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
Nicholas J CroucherMRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK.ORCID http://orcid.org/0000-0001-6303-8768
Rebecca A GladstoneParasites and Microbes, Wellcome Sanger Institute, Cambridge, CB10 1SA, UK.
Hester J BootsmaCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, 3721 MA, The Netherlands.
Nynke Y RotsCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, 3721 MA, The Netherlands.
Alienke J Wijmega-MonsuurCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, 3721 MA, The Netherlands.
Elisabeth A M SandersCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, 3721 MA, The Netherlands.
Krzysztof TrzcińskiDepartment of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, 3508 AB, The Netherlands.
Anne L WyllieDepartment of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, 3508 AB, The Netherlands.
Aeilko H ZwindermanAmsterdam UMC, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Public Health, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.ORCID http://orcid.org/0000-0003-0361-3139
Leonard H van den BergDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
Wouter van RheenenDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.ORCID http://orcid.org/0000-0002-5860-1533
Jan H VeldinkDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
Zitta B HarboeDepartment of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, DK-2300, Denmark.
Lene F LundboDepartment of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, 2650, Denmark.
Lisette C P G M de GrootDepartment of Human Nutrition, Wageningen University, P.O. Box 17, 6700 AA, Wageningen, The Netherlands.ORCID http://orcid.org/0000-0003-2778-2789
Natasja M van SchoorAmsterdam UMC, VU University, Department of Epidemiology and Biostatistics, Amsterdam Public Health, Van der Boechorststraat 7, Amsterdam, 1007 MB, The Netherlands.
Nathalie van der VeldeAmsterdam UMC, University of Amsterdam, Department of Internal Medicine, Geriatrics, Amsterdam Public Health, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
Lars H ÄngquistCenter for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, DK-2000, Denmark.
Thorkild I A SørensenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Copenhagen, DK-2200, Denmark.ORCID http://orcid.org/0000-0003-4821-430X
Ellen A NohrInstitute of Clinical Research, University of Southern Denmark, Odense, DK-5000, Denmark.
Alexander J MentzerWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.ORCID http://orcid.org/0000-0002-4502-2209
Tara C MillsWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
Julian C KnightWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.ORCID http://orcid.org/0000-0002-0377-5536
Mignon du PlessisSchool of Pathology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2000, South Africa.ORCID http://orcid.org/0000-0001-9186-0679
Susan NzenzeSchool of Pathology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2000, South Africa.
Jeffrey N WeiserDepartment of Microbiology, New York University School of Medicine, New York, NY, 10016, USA.ORCID http://orcid.org/0000-0001-7168-8090
Julian ParkhillParasites and Microbes, Wellcome Sanger Institute, Cambridge, CB10 1SA, UK.ORCID http://orcid.org/0000-0002-7069-5958
Shabir MadhiNational Institute for Communicable Diseases, Johannesburg, 2192, South Africa.
Thomas BenfieldDepartment of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, 2650, Denmark.
Anne von GottbergSchool of Pathology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2000, South Africa.
Arie van der EndeAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology, Amsterdam Infection and Immunity, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
Matthijs C BrouwerAmsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
Jeffrey C BarrettParasites and Microbes, Wellcome Sanger Institute, Cambridge, CB10 1SA, UK.ORCID http://orcid.org/0000-0002-1152-370X
Stephen D BentleyParasites and Microbes, Wellcome Sanger Institute, Cambridge, CB10 1SA, UK. sdb@sanger.ac.uk.
Diederik van de BeekAmsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands. d.vandebeek@amc.uva.nl.ORCID http://orcid.org/0000-0002-4571-044X
Wellcome Sanger Institute · GBAmsterdam Neuroscience · NLNational Institute for Public Health and the Environment · NLAmsterdam University Medical Centers · NLCentre for Human Genetics · GBUniversity Medical Center Utrecht · NLUniversity of Copenhagen · DKUniversity of the Witwatersrand · ZAErasmus MC · NLFrederiksberg Hospital · DKImperial College London · GBNational Institute for Communicable DiseasesNew York University · USStatens Serum Institut · DKUniversity of Southern Denmark · DKWageningen University & Research · NLWilhelmina Children's Hospital · NLYale University · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MROLE OF OPACITY VARIATION IN PNEUMOCOCCAL PATHOGENESISR01AI038446 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WEISER, JEFFREY NEAL · 1996 to 2019
$7.4MMechanisms of Pneumococcal Persistence During CarriageR37AI038446 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jeffrey Neal Weiser · 2020 to 2026
$3.8MBACTERIAL PHOSPHORYLCHOLINE AND PATHOGENESISR01AI044231 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WEISER, JEFFREY NEAL · 1999 to 2009
$2.6MEarly Events in Pneumococcal ColonizationR01AI105168 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WEISER, JEFFREY NEAL · 2014 to 2018
$2.1MMedical Research Council MR/R015600/1NCATS NIH HHS UL1 TR001863NIAID NIH HHS R01 AI038446NIAID NIH HHS R01 AI044231NIAID NIH HHS R01 AI105168NIAID NIH HHS R37 AI038446Wellcome Trust 098051Wellcome Trust 204969/Z/16/Z
Abstract
Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.
Indexed as
Genetic Predisposition to DiseaseAdultAgedBacterial ProteinsFemaleGenetic VariationGenome, BacterialGenome, HumanGenome-Wide Association StudyHost-Pathogen InteractionsHumansMaleMeningitis, PneumococcalMiddle AgedProspective StudiesProteinsBacterial ProteinsCCDC33 protein, humanProteinsSpsA protein, Streptococcus pneumoniae
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