Evidence map›Paper›PMID 36709579›Full record

ArticleEBioMedicine2023

A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates.

Stéphanie Pons, Eric Frapy, Youssouf Sereme, Charlotte Gaultier, François Lebreton, Andrea Kropec, Olga Danilchanka, Laura Schlemmer, Cécile Schrimpf, Margaux Allain and 11 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.7field-weighted citation impact, top 7% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 2 countries.

Stéphanie PonsDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Anesthesiology and Critical Care, Sorbonne University, GRC 29, AP-HP, DMU DREAM, Pitié-Salpêtrière, Paris, France.
Eric FrapyCNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France; Faculté de Médecine, University of Paris City, Paris, France.
Youssouf SeremeCNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France; Faculté de Médecine, University of Paris City, Paris, France.
Charlotte GaultierDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
François LebretonDepartment of Ophthalmology and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02114, USA.
Andrea KropecDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Olga DanilchankaDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Laura SchlemmerCNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France.
Cécile SchrimpfCNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France.
Margaux AllainCNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France.
François AngoulvantAssistance Publique - Hôpitaux de Paris, Pediatric Emergency Department, Necker-Enfants Malades University Hospital, University of Paris City, Paris, France; INSERM, Centre de Recherche des Cordeliers, UMRS 1138, Sorbonne Université, Université de Paris, Paris, France.
Hervé LecuyerCNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France; Faculté de Médecine, University of Paris City, Paris, France; Department of Clinical Microbiology, Fédération Hospitalo-Universitaire Prématurité (FHU PREMA), Necker-Enfants Malades University Hospital, University of Paris City, Paris, France.
Stéphane BonacorsiE IAME, UMR 1137, INSERM, Université de Paris, AP-HP, Paris, France; Laboratoire de Microbiologie, Hôpital Robert Debré, AP-HP, Paris, France.
Hugues AschardCentre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, France; Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
Harry SokolGastroenterology Department, Sorbonne University, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, F-75012 Paris, France; INRA, UMR1319 Micalis & AgroParisTech, Jouy en Josas, France; Paris Centre for Microbiome Medicine FHU, Paris, France.
Colette Cywes-BentleyDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
John J MekalanosDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Thomas GuillardDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Université de Reims Champagne-Ardenne, SFR CAP-Santé, Inserm UMR-S 1250 P3Cell, Reims, France; Laboratoire de Bactériologie-Virologie-Hygiène Hospitalière-Parasitologie-Mycologie, CHU, Reims, France.
Gerald B PierDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Damien RouxDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Université de Paris, INSERM, UMR 1137 IAME, F-75018 Paris, France; AP-HP, Médecine Intensive Réanimation, Hôpital Louis Mourier, F-92700 Colombes, France.
David SkurnikDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; CNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France; Faculté de Médecine, University of Paris City, Paris, France; Department of Clinical Microbiology, Fédération Hospitalo-Universitaire Prématurité (FHU PREMA), Necker-Enfants Malades University Hospital, University of Paris City, Paris, France. Electronic address: david.skurnik@inserm.fr.
Brigham and Women's Hospital · USCentre National de la Recherche Scientifique · FRHarvard University · USInserm · FRDélégation Paris 5 · FRHôpital Necker-Enfants Malades · FR

Funding

COORDINATE REGULATION OF BACTERIAL VIRULENCE FACTORSR01AI026289 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MEKALANOS, JOHN JOSEPH · 1988 to 2018
$8.3M
Virulence and Immunity to StaphylcocciR01AI046706 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI PIER, GERALD B · 2001 to 2010
$4.1M
NIAID NIH HHS R01 AI026289NIAID NIH HHS R01 AI046706
6 · The paper itself

Abstract

backgroundWorldwide, Escherichia coli is the leading cause of neonatal Gram-negative bacterial meningitis, but full understanding of the pathogenesis of this disease is not yet achieved. Moreover, to date, no vaccine is available against bacterial neonatal meningitis.

methodsHere, we used Transposon Sequencing of saturated banks of mutants (TnSeq) to evaluate E. coli K1 genetic fitness in murine neonatal meningitis. We identified E. coli K1 genes encoding for factors important for systemic dissemination and brain infection, and focused on products with a likely outer-membrane or extra-cellular localization, as these are potential vaccine candidates. We used in vitro and in vivo models to study the efficacy of active and passive immunization.

resultsWe selected for further study the conserved surface polysaccharide Poly-β-(1-6)-N-Acetyl Glucosamine (PNAG), as a strong candidate for vaccine development. We found that PNAG was a virulence factor in our animal model. We showed that both passive and active immunization successfully prevented and/or treated meningitis caused by E. coli K1 in neonatal mice. We found an excellent opsonophagocytic killing activity of the antibodies to PNAG and in vitro these antibodies were also able to decrease binding, invasion and crossing of E. coli K1 through two blood brain barrier cell lines. Finally, to reinforce the potential of PNAG as a vaccine candidate in bacterial neonatal meningitis, we demonstrated that Group B Streptococcus, the main cause of neonatal meningitis in developed countries, also produced PNAG and that antibodies to PNAG could protect in vitro and in vivo against this major neonatal pathogen.

interpretationAltogether, these results indicate the utility of a high-throughput DNA sequencing method to identify potential immunotherapy targets for a pathogen, including in this study a potential broad-spectrum target for prevention of neonatal bacterial infections. FUNDINGS: ANR Seq-N-Vaq, Charles Hood Foundation, Hearst Foundation, and Groupe Pasteur Mutualité.

Indexed as

Escherichia coliMeningitis, BacterialAnimalsAntibodies, BacterialBacteriaHigh-Throughput Nucleotide SequencingImmunotherapyMiceAntibodies, BacterialE. coli K1High-throughput sequencingNeonatal meningitisPNAGVaccine

Identifiers

PMID36709579
PMCPMC9900374
OpenAlexW4318243625

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.