Welcome on the Necker-Enfants Malades Institute website

Understanding the mechanisms by which bacteria disseminate in the host beyond the port-of-entry

from basic science:
  • bacteria
  • pathogenesis
to the translational research:
  • anti-infective
  • vaccine
  • diagnostic
Xavier Nassif
Alain Charbit
Pathogenesis of systemic infections

Xavier Nassif, M.D-PhD. is Professor of Microbiology at the Medical School Paris Descartes. He obtained is Medical Degree in 1987 and a PhD at the Pasteur Institute in 1989. After a postdoctoral fellowship he joined in 1992 the « Faculté de Médecine Paris Descartes » where he is heading the Clinical Microbiology Laboratory and the Institut Necker-Enfants Malades.

Alain Charbit, PhD, is Research Director (DR1) from the CNRS. He obtained a PhD at the Pasteur Institute in 1990. He was recruited by the CNRS in 1997. After 15 years at the Pasteur Institute, he joined in 1998 the « Faculté de Médecine Paris Descartes » where he is currently co-heading team 11 at the Institut Necker-Enfants Malades.

Focus

Bacterial systemic infections remain a public health concern in the developed world, Our long term goal is a better understanding of the pathogenesis of these infections in order to identify new targets for prevention and treatment.

Introduction

Systemic infections are characterized by the ability of infecting pathogens to colonize and to disseminate from their port-of-entry into the bloodstream. Two types of bacterial pathogens disseminate beyond their port-of-entry:

  1. the extra cellular pathogens that can survive in the extracellular fluids and have developed attributes that prevent phagocytosis by polymorphonuclear cells and killing by the serum. These bacteria are essentially those responsible for sepsis that remains a life-threatening condition and a major contributor of public health and economic burden in the industrialized world. These pathogens are in direct contact with endothelial cells. Much remain to be understood on the mechanisms and consequences of this bacterial interaction with the capillaries, even though this interaction is a prerequisite for metastatic dissemination (crossing of the blood brain barrier for example).
  2. The intracellular pathogens that disseminate in the body using a Trojan horse such as macrophages. The mechanisms by which these latter pathogens resist to the bactericidal Intracellular environment have long been studied. On the other hand, these pathogens often critically rely on acquisition of host-derived nutrients for the development of a successful infection. Since nutrient availability depends on host metabolism and differs depending on localization within tissues and varies over the course of infection, intracellular pathogens have had to adapt their metabolism to these host metabolic rearrangements.

Research objectives

Four main research axes are being pursued.

  • The first approach focuses on the mechanisms and consequences of the interaction of extra-cellular bacterial pathogens with endothelial cells using Neisseria meningtidis as paradigm. This pathogen following bloodstream invasion from the nasopharynx establishes a strong interaction with the capillaries. This interaction is associated with the occurrence of meningitis and Purpura fulminans. Our objectives are to provide a coherent picture of meningococcal pathogenesis by dissecting the interaction between meningococci and endothelial cells at the molecular, cellular, and tissular levels.
  • The second approach consists in deciphering the molecular bases of the host-pathogen metabolic interplay of an intracellular bacterial pathogen, using Francisella tularensis as a model organism. The virulence of this Gram-negative intracellular bacterium, causative agent of the zoonotic disease tularemia, is tightly linked to its capacity to multiply in the cytosolic compartment of infected macrophages. Our objectives are: i) to understand how the metabolism of this bacteria has evolved to adapt to its intracellular niche; and ii) to define how the metabolism of the host itself is modified in response to the infection.
  • The third approach aims at providing new insights on Staphylococcus aureus pathogenesis, which is one of the deadliest bacteria in Western countries. We are particularly committed to the study of virulence factors associated with chronic infections and we have implemented translational research projects involving cohorts of children with chronic S. aureus infections (cystic fibrosis and epidermolysis bullosa). Bacterial adaptation explains why bacteria persist at infected sites despite antibiotic treatment. This project will provide an understanding of the molecular mechanisms of adaptation of S. aureus when subjected to high in vivo selection pressure and the consequences on the host inflammatory response.
    Our two main objectives are: i) to identify genetic mutations modulating toxicity and inflammation, through an unbiased proteogenomic analysis of adapted S. aureus isolates and ii) to study the impact of S. aureus adaptation in vitro and in vivo, with a focus on the host inflammatory response and cytokine secretion.
  • The fourth axis is "Genomic approaches to microbial pathogenesis and vaccine development". In developed countries, 20% of the bacterial meningitis in neonates is due to Escherichia coli K1. We use TnSeq to (i) identify and understand the genes and regulatory genetic elements contributing to optimal fitness of E. coli K1 from GI tract colonization, to crossing of the blood brain barrier and, (ii), identify and develop new vaccine candidates via a process we have called TnSeq vaccinology. This approach exploits the TnSeq tool to test the effect of host immunity, induced by vaccination with a broadly-protective immunogen such as antibiotic-killed cells, on selection of strains with Tn-interrupted genes. This approach should impact all types of vaccine antigens, not just proteins, a limitation of current antigen identification systems such as reverse vaccinology.

We are member of the Bacteriophage Network France: https://site.phages.fr/

Cinq publications originales majeures

  • Le Guennec L, Virion Z, Bouzinba-Ségard H, Robbe-Masselot C, Léonard R, Nassif X, Bourdoulous S, Coureuil M. Receptor recognition by meningococcal type IV pili relies on a specific complex N-glycan. Proc Natl Acad Sci U S A. 2020 Feb 4;117(5):2606-2612. doi: 10.1073/pnas.1919567117. Epub 2020 Jan 21. doi: 10.1073/pnas.1919567117
  • Virion Z, Doly S, Saha K, Lambert M, Guillonneau F, Bied C, Duke RM, Rudd PM, Robbe-Masselot C, Nassif X, Coureuil M, Marullo S. (2019). Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili. Nat Commun. 2019 Oct 18;10(1):4752. doi: 10.1038/s41467-019-12685-6
  • Aschard H, Laville V, Tchetgen ET, Knights D, Imhann F, Seksik P, Zaitlen N, Silverberg MS, Cosnes J, Weersma RK, Xavier R, Beaugerie L, Skurnik D, Sokol H. Genetic effects on the commensal microbiota in inflammatory bowel disease patients. PLoS Genet. 2019 Mar 8;15(3):e1008018. doi: 10.1371/journal.pgen.1008018. eCollection 2019 Mar. doi: 10.1371/journal.pgen.1008018
  • Tan X, Coureuil M, Ramond E, Euphrasie D, Dupuis M, Tros F, Meyer J, Nemazanyy I, Chhuon C, Guerrera IC, Ferroni A, Sermet-Gaudelus I, Nassif X, Charbit A, Jamet A. Chronic Staphylococcus aureus Lung Infection Correlates With Proteogenomic and Metabolic Adaptations Leading to an Increased Intracellular Persistence. Clin Infect Dis. 2019 Nov 13;69(11):1937-1945. doi: 10.1093/cid/ciz106
  • Ziveri J, Tros F, Guerrera IC, Chhuon C, Audry M, Dupuis M, Barel M, Korniotis S, Fillatreau S, Gales L, Cahoreau E, Charbit A. The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella. Nat Commun. 2017 Oct 11;8(1):853. doi: 10.1038/s41467-017-00889-7
  • Liste des publications

    2021

  • Barnier, JP, Meyer, J, Kolappan, S, Bouzinba-Ségard, H, Gesbert, G, Jamet, A et al.. The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus. Proc Natl Acad Sci U S A. 2021;118 (45):. doi: 10.1073/pnas.2109364118. PubMed PMID:34725157 .
  • Rytter, H, Jamet, A, Ziveri, J, Ramond, E, Coureuil, M, Lagouge-Roussey, P et al.. The pentose phosphate pathway constitutes a major metabolic hub in pathogenic Francisella. PLoS Pathog. 2021;17 (8):e1009326. doi: 10.1371/journal.ppat.1009326. PubMed PMID:34339477 PubMed Central PMC8360588.
  • Ramond, E, Jamet, A, Ding, X, Euphrasie, D, Bouvier, C, Lallemant, L et al.. Reactive Oxygen Species-Dependent Innate Immune Mechanisms Control Methicillin-Resistant Staphylococcus aureus Virulence in the Drosophila Larval Model. mBio. 2021;12 (3):e0027621. doi: 10.1128/mBio.00276-21. PubMed PMID:34126772 PubMed Central PMC8262968.
  • Regnault, B, Evrard, B, Plu, I, Dacheux, L, Troadec, E, Cozette, P et al.. First case of lethal encephalitis in Western Europe due to European bat lyssavirus type 1. Clin Infect Dis. 2021; :. doi: 10.1093/cid/ciab443. PubMed PMID:33991184 .
  • Barnier, JP, Euphrasie, D, Join-Lambert, O, Audry, M, Schonherr-Hellec, S, Schmitt, T et al.. Type IV pilus retraction enables sustained bacteremia and plays a key role in the outcome of meningococcal sepsis in a humanized mouse model. PLoS Pathog. 2021;17 (2):e1009299. doi: 10.1371/journal.ppat.1009299. PubMed PMID:33592056 PubMed Central PMC7909687.
  • Jamet, A, Guglielmini, J, Brancotte, B, Coureuil, M, Euphrasie, D, Meyer, J et al.. High-Resolution Typing of Staphylococcus epidermidis Based on Core Genome Multilocus Sequence Typing To Investigate the Hospital Spread of Multidrug-Resistant Clones. J Clin Microbiol. 2021;59 (3):. doi: 10.1128/JCM.02454-20. PubMed PMID:33328176 PubMed Central PMC8106705.

  • 2020

  • Meningococcal disease: A paradigm of type-IV pilus dependent pathogenesis.Dos Santos Souza I, Maïssa N, Ziveri J, Morand PC, Coureuil M, Nassif X, Bourdoulous S. Cell Microbiol. 2020 Apr;22(4):e13185. doi: 10.1111/cmi.13185.PMID: 32185901Review.
  • Clinical and virological responses to a broad-spectrum human monoclonal antibody in an influenza virus challenge study.Sloan SE, Szretter KJ, Sundaresh B, Narayan KM, Smith P, Skurnik D, Bedard S, Trevejo JM, Oldach D, Shriver Z. Antiviral Res. 2020 Mar 6:104763. doi: 0.1016/j.antiviral.2020.104763. Online ahead of print.PMID: 32151645
  • Receptor recognition by meningococcal type IV pili relies on a specific complex N-glycan. Le Guennec L, Virion Z, Bouzinba-Ségard H, Robbe-Masselot C, Léonard R, Nassif X, Bourdoulous S, Coureuil M. Proc Natl Acad Sci U S A. 2020 Feb 4;117(5):2606-2612. doi: 10.1073/pnas.1919567117. Epub 2020 Jan 21.PMID: 31964828
  • Strategies used by bacterial pathogens to cross the blood-brain barrier. Le Guennec L, Coureuil M, Nassif X, Bourdoulous S. Cell Microbiol. 2020 Jan;22(1):e13132. doi: 10.1111/cmi.13132. Epub 2019 Nov 10.PMID: 31658405 Review.
  • Multitasking Actors of Staphylococcus aureus Metabolism and Virulence. Tan X, Coureuil M, Charbit A, Jamet A. Trends Microbiol. 2020 Jan;28(1):6-9. doi: 10.1016/j.tim.2019.10.013. Epub 2019 Nov 18.PMID: 31753539
  • A role for Taok2 in Listeria monocytogenes vacuolar escape. JJ, Morel C, Lopez-Montero N, Ziveri J, Rolland S, Grenier T, Aulner N, Danckaert A, Charbit A, Enninga J, Cossart P, Pizarro-Cerdá J.J Infect Dis. 2020 Jun 25:jiaa367. doi: 10.1093/infdis/jiaa367.
  • Skurnik, D, Rybak, A, Yang, DD, Pons, S, Guedj, R, Levy, C et al.. Unexpected lessons from the COVID-19 lockdowns in France: Low impact of school opening on common communicable pediatric airborne diseases. Clin Infect Dis. 2020; :. doi: 10.1093/cid/ciaa1899. PubMed PMID:33373441 PubMed Central PMC7799226.
  • Skurnik, D, Rybak, A, Yang, DD, Pons, S, Guedj, R, Levy, C et al.. Unexpected lessons from the COVID-19 lockdowns in France: Low impact of school opening on common communicable pediatric airborne diseases. Clin Infect Dis. 2020; :. doi: 10.1093/cid/ciaa1899. PubMed PMID:33373441 PubMed Central PMC7799226.
  • Rytter, H, Jamet, A, Coureuil, M, Charbit, A, Ramond, E. Which Current and Novel Diagnostic Avenues for Bacterial Respiratory Diseases?. Front Microbiol. 2020;11 :616971. doi: 10.3389/fmicb.2020.616971. PubMed PMID:33362754 PubMed Central PMC7758241.
  • Jamet, A, Guglielmini, J, Brancotte, B, Coureuil, M, Euphrasie, D, Meyer, J et al.. High resolution typing of Staphylococcus epidermidis based on cgMLST to investigate the hospital spread of multidrug resistant clones. J Clin Microbiol. 2020; :. doi: 10.1128/JCM.02454-20. PubMed PMID:33328176 .
  • Yang, DD, Ouldali, N, Gajdos, V, Thomas-Sertillanges, R, Vasante, L, Skurnik, D et al.. Common pediatric respiratory infectious diseases may serve as an early predictor for SARS-CoV-2 new wave of infections. Clin Infect Dis. 2020; :. doi: 10.1093/cid/ciaa1359. PubMed PMID:32894752 PubMed Central PMC7499521.
  • Angoulvant, F, Ouldali, N, Yang, DD, Filser, M, Gajdos, V, Rybak, A et al.. COVID-19 pandemic: Impact caused by school closure and national lockdown on pediatric visits and admissions for viral and non-viral infections, a time series analysis. Clin Infect Dis. 2020; :. doi: 10.1093/cid/ciaa710. PubMed PMID:32492117 PubMed Central PMC7314162.
  • Marullo, S, Doly, S, Saha, K, Enslen, H, Scott, MGH, Coureuil, M et al.. Mechanical GPCR Activation by Traction Forces Exerted on Receptor N-Glycans. ACS Pharmacol Transl Sci. 2020;3 (2):171-178. doi: 10.1021/acsptsci.9b00106. PubMed PMID:32296760 PubMed Central PMC7155188.
  • 2019

  • Airway Mucus Restricts Neisseria meningitidis Away from Nasopharyngeal Epithelial Cells and Protects the Mucosa from Inflammation.
    Audry M, Robbe-Masselot C, Barnier JP, Gachet B, Saubaméa B, Schmitt A, Schönherr-Hellec S, Léonard R, Nassif X, Coureuil M.
    mSphere. 2019 Dec 4;4(6):e00494-19. doi: 10.1128/mSphere.00494-19.PMID: 31801841Free PMC article.
  • Author Correction: Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis.
    Simonin J, Bille E, Crambert G, Noel S, Dreano E, Edwards A, Hatton A, Pranke I, Villeret B, Cottart CH, Vrel JP, Urbach V, Baatallah N, Hinzpeter A, Golec A, Touqui L, Nassif X, Galietta LJV, Planelles G, Sallenave JM, Edelman A, Sermet-Gaudelus I.
    Sci Rep. 2019 Nov 21;9(1):17535. doi: 10.1038/s41598-019-54253-4.PMID: 31754179-Free PMC article.
  • Multitasking Actors of Staphylococcus aureus Metabolism and Virulence.
    Tan X, Coureuil M, Charbit A, Jamet A.
    Trends Microbiol. 2020 Jan;28(1):6-9. doi: 10.1016/j.tim.2019.10.013. Epub 2019 Nov 18.PMID: 31753539
  • Pivotal Role of Mitochondria in Macrophage Response to Bacterial Pathogens.
    Ramond E, Jamet A, Coureuil M, Charbit A.
    Front Immunol. 2019 Oct 23;10:2461. doi: 10.3389/fimmu.2019.02461. eCollection 2019.PMID: 31708919Free PMC article.Review.
  • Strategies used by bacterial pathogens to cross the blood-brain barrier.
    Le Guennec L, Coureuil M, Nassif X, Bourdoulous S.
    Cell Microbiol. 2020 Jan;22(1):e13132. doi: 10.1111/cmi.13132. Epub 2019 Nov 10.PMID: 31658405Review.
  • Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili.
    Virion Z, Doly S, Saha K, Lambert M, Guillonneau F, Bied C, Duke RM, Rudd PM, Robbe-Masselot C, Nassif X, Coureuil M, Marullo S.
    Nat Commun. 2019 Oct 18;10(1):4752. doi: 10.1038/s41467-019-12685-6.PMID: 31628314Free PMC article.
  • Critical Role of a Sheath Phosphorylation Site On the Assembly and Function of an Atypical Type VI Secretion System.
    Ziveri J, Chhuon C, Jamet A, Rytter H, Prigent G, Tros F, Barel M, Coureuil M, Lays C, Henry T, Keep NH, Guerrera IC, Charbit A.
    Mol Cell Proteomics. 2019 Dec;18(12):2418-2432. doi: 10.1074/mcp.RA119.001532. Epub 2019 Oct 2.PMID: 31578219
  • Transketolase of Staphylococcus aureus in the Control of Master Regulators of Stress Response During Infection.
    Tan X, Ramond E, Jamet A, Barnier JP, Decaux-Tramoni B, Dupuis M, Euphrasie D, Tros F, Nemazanyy I, Ziveri J, Nassif X, Charbit A, Coureuil M.
    J Infect Dis. 2019 Nov 6;220(12):1967-1976. doi: 10.1093/infdis/jiz404.PMID: 31420648
  • Molecular interactions between Neisseria meningitidis and its human host.
    Coureuil M, Jamet A, Bille E, Lécuyer H, Bourdoulous S, Nassif X.
    Cell Microbiol. 2019 Nov;21(11):e13063. doi: 10.1111/cmi.13063. Epub 2019 Jun 13.PMID: 31167044Free PMC article.
  • Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis.
    Simonin J, Bille E, Crambert G, Noel S, Dreano E, Edwards A, Hatton A, Pranke I, Villeret B, Cottart CH, Vrel JP, Urbach V, Baatallah N, Hinzpeter A, Golec A, Touqui L, Nassif X, Galietta LJV, Planelles G, Sallenave JM, Edelman A, Sermet-Gaudelus I.
    Sci Rep. 2019 Apr 24;9(1):6516. doi: 10.1038/s41598-019-42751-4.PMID: 31019198Free PMC article.
  • Fulminant arterial vasculitis as an unusual complication of disseminated staphylococcal disease due to the emerging CC1 methicillin-susceptible Staphylococcus aureus clone: a case report.
    Vidal C, Moulin F, Nassif X, Galmiche L, Borgel D, Charbit A, Picard C, Mira JP, Lortholary O, Jamet A, Toubiana J.
    BMC Infect Dis. 2019 Apr 3;19(1):302. doi: 10.1186/s12879-019-3933-3.PMID: 30943907Free PMC article.
  • Methods to Study the Roles of β-Arrestins in Meningococcal Signaling.
    Virion Z, Marullo S, Coureuil M.
    Methods Mol Biol. 2019;1957:325-334. doi: 10.1007/978-1-4939-9158-7_20.PMID: 30919363
  • Targeting Type IV pili as an antivirulence strategy against invasive meningococcal disease.
    Denis K, Le Bris M, Le Guennec L, Barnier JP, Faure C, Gouge A, Bouzinba-Ségard H, Jamet A, Euphrasie D, Durel B, Barois N, Pelissier P, Morand PC, Coureuil M, Lafont F, Join-Lambert O, Nassif X, Bourdoulous S.
    Nat Microbiol. 2019 Jun;4(6):972-984. doi: 10.1038/s41564-019-0395-8. Epub 2019 Mar 25.PMID: 30911127
  • Genetic effects on the commensal microbiota in inflammatory bowel disease patients.
    Aschard H, Laville V, Tchetgen ET, Knights D, Imhann F, Seksik P, Zaitlen N, Silverberg MS, Cosnes J, Weersma RK, Xavier R, Beaugerie L, Skurnik D, Sokol H.
    PLoS Genet. 2019 Mar 8;15(3):e1008018. doi: 10.1371/journal.pgen.1008018. eCollection 2019 Mar.PMID: 30849075Free PMC article.
  • Chronic Staphylococcus aureus Lung Infection Correlates With Proteogenomic and Metabolic Adaptations Leading to an Increased Intracellular Persistence.
    Tan X, Coureuil M, Ramond E, Euphrasie D, Dupuis M, Tros F, Meyer J, Nemazanyy I, Chhuon C, Guerrera IC, Ferroni A, Sermet-Gaudelus I, Nassif X, Charbit A, Jamet A.
    Clin Infect Dis. 2019 Nov 13;69(11):1937-1945. doi: 10.1093/cid/ciz106.PMID: 30753350
  • [Meningococcus purpura fulminans, a partially solved mystery].
    Lécuyer H, Nassif X, Coureuil M.
    Med Sci (Paris). 2018 Dec;34(12):1038-1041. doi: 10.1051/medsci/2018288. Epub 2019 Jan 9.PMID: 30623761French.No abstract available.
  • 2018

  • A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses.
    Le Gallou S, Zhou Z, Thai LH, Fritzen R, de Los Aires AV, Mégret J, Yu P, Kitamura D, Bille E, Tros F, Nassif X, Charbit A, Weller S, Weill JC, Reynaud CA.
    J Exp Med. 2018 Aug 6;215(8):2035-2053. doi: 10.1084/jem.20180977. Epub 2018 Jun 29.PMID: 29959173Free PMC article.
  • An ADAM-10 dependent EPCR shedding links meningococcal interaction with endothelial cells to purpura fulminans.
    Lécuyer H, Virion Z, Barnier JP, Matczak S, Bourdoulous S, Bianchini E, Saller F, Borgel D, Nassif X, Coureuil M.
    PLoS Pathog. 2018 Apr 9;14(4):e1006981. doi: 10.1371/journal.ppat.1006981. eCollection 2018 Apr.PMID: 29630665Free PMC article.
  • The absence of N-acetylglucosamine in wall teichoic acids of Listeria monocytogenes modifies biofilm architecture and tolerance to rinsing and cleaning procedures.
    Brauge T, Faille C, Sadovskaya I, Charbit A, Benezech T, Shen Y, Loessner MJ, Bautista JR, Midelet-Bourdin G.
    PLoS One. 2018 Jan 10;13(1):e0190879. doi: 10.1371/journal.pone.0190879. eCollection 2018.PMID: 29320565Free PMC article.
  • 2017

  • Type I interferon-mediated autoinflammation due to DNase II deficiency.
    Rodero MP, Tesser A, Bartok E, Rice GI, Della Mina E, Depp M, Beitz B, Bondet V, Cagnard N, Duffy D, Dussiot M, Frémond ML, Gattorno M, Guillem F, Kitabayashi N, Porcheray F, Rieux-Laucat F, Seabra L, Uggenti C, Volpi S, Zeef LAH, Alyanakian MA, Beltrand J, Bianco AM, Boddaert N, Brouzes C, Candon S, Caorsi R, Charbit M, Fabre M, Faletra F, Girard M, Harroche A, Hartmann E, Lasne D, Marcuzzi A, Neven B, Nitschke P, Pascreau T, Pastore S, Picard C, Picco P, Piscianz E, Polak M, Quartier P, Rabant M, Stocco G, Taddio A, Uettwiller F, Valencic E, Vozzi D, Hartmann G, Barchet W, Hermine O, Bader-Meunier B, Tommasini A, Crow YJ.
    Nat Commun. 2017 Dec 19;8(1):2176. doi: 10.1038/s41467-017-01932-3.PMID: 29259162Free PMC article.
  • Antibacterial Toxins: Gram-Positive Bacteria Strike Back!
    Jamet A, Charbit A, Nassif X.
    Trends Microbiol. 2018 Feb;26(2):89-91. doi: 10.1016/j.tim.2017.11.003. Epub 2017 Nov 21.PMID: 29174101
  • Peripheral blood vessels are a niche for blood-borne meningococci.
    Capel E, Barnier JP, Zomer AL, Bole-Feysot C, Nussbaumer T, Jamet A, Lécuyer H, Euphrasie D, Virion Z, Frapy E, Pélissier P, Join-Lambert O, Rattei T, Bourdoulous S, Nassif X, Coureuil M.
    Virulence. 2017 Nov 17;8(8):1808-1819. doi: 10.1080/21505594.2017.1391446. Epub 2017 Nov 27.PMID: 29099305Free PMC article.
  • Covariate selection for association screening in multiphenotype genetic studies.
    Aschard H, Guillemot V, Vilhjalmsson B, Patel CJ, Skurnik D, Ye CJ, Wolpin B, Kraft P, Zaitlen N.
    Nat Genet. 2017 Dec;49(12):1789-1795. doi: 10.1038/ng.3975. Epub 2017 Oct 16.PMID: 29038595Free PMC article.
  • The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella.
    Ziveri J, Tros F, Guerrera IC, Chhuon C, Audry M, Dupuis M, Barel M, Korniotis S, Fillatreau S, Gales L, Cahoreau E, Charbit A.
    Nat Commun. 2017 Oct 11;8(1):853. doi: 10.1038/s41467-017-00889-7.PMID: 29021545Free PMC article.
  • Cryoelectron Microscopy Reconstructions of the Pseudomonas aeruginosa and Neisseria gonorrhoeae Type IV Pili at Sub-nanometer Resolution.
    Wang F, Coureuil M, Osinski T, Orlova A, Altindal T, Gesbert G, Nassif X, Egelman EH, Craig L.
    Structure. 2017 Sep 5;25(9):1423-1435.e4. doi: 10.1016/j.str.2017.07.016.PMID: 28877506
  • A widespread family of polymorphic toxins encoded by temperate phages.
    Jamet A, Touchon M, Ribeiro-Gonçalves B, Carriço JA, Charbit A, Nassif X, Ramirez M, Rocha EPC.
    BMC Biol. 2017 Aug 29;15(1):75. doi: 10.1186/s12915-017-0415-1.PMID: 28851366Free PMC article.
  • Intracellular Survival of Staphylococcus aureus in Endothelial Cells: A Matter of Growth or Persistence.
    Rollin G, Tan X, Tros F, Dupuis M, Nassif X, Charbit A, Coureuil M.
    Front Microbiol. 2017 Jul 19;8:1354. doi: 10.3389/fmicb.2017.01354. eCollection 2017.PMID: 28769913Free PMC article.
  • Intradermal Immunization with rAAV1 Vector Induces Robust Memory CD8+ T Cell Responses Independently of Transgene Expression in DCs.
    Ghenassia A, Gross DA, Lorain S, Tros F, Urbain D, Benkhelifa-Ziyyat S, Charbit A, Davoust J, Chappert P.
    Mol Ther. 2017 Oct 4;25(10):2309-2322. doi: 10.1016/j.ymthe.2017.06.019. Epub 2017 Jul 15.PMID: 28720467Free PMC article.
  • A virulence-associated filamentous bacteriophage of Neisseria meningitidis increases host-cell colonisation.
    Bille E, Meyer J, Jamet A, Euphrasie D, Barnier JP, Brissac T, Larsen A, Pelissier P, Nassif X.
    PLoS Pathog. 2017 Jul 13;13(7):e1006495. doi: 10.1371/journal.ppat.1006495. eCollection 2017 Jul.PMID: 28704569Free PMC article.
  • Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4.
    Maïssa N, Covarelli V, Janel S, Durel B, Simpson N, Bernard SC, Pardo-Lopez L, Bouzinba-Ségard H, Faure C, Scott MGH, Coureuil M, Morand PC, Lafont F, Nassif X, Marullo S, Bourdoulous S.
    Nat Commun. 2017 Jun 1;8:15764. doi: 10.1038/ncomms15764.PMID: 28569760Free PMC article.
  • Importance of Metabolic Adaptations in Francisella Pathogenesis.
    Ziveri J, Barel M, Charbit A.
    Front Cell Infect Microbiol. 2017 Mar 28;7:96. doi: 10.3389/fcimb.2017.00096. eCollection 2017.PMID: 28401066Free PMC article.Review.
  • Role of Glycosylation/Deglycolysation Processes in Francisella tularensis Pathogenesis.
    Barel M, Charbit A.
    Front Cell Infect Microbiol. 2017 Mar 21;7:71. doi: 10.3389/fcimb.2017.00071. eCollection 2017.PMID: 28377902Free PMC article.Review.
  • Pathogenesis of meningococcal purpura fulminans.
    Lécuyer H, Borgel D, Nassif X, Coureuil M.
    Pathog Dis. 2017 Apr 1;75(3). doi: 10.1093/femspd/ftx027.PMID: 28334263Review.
  • A journey into the brain: insight into how bacterial pathogens cross blood-brain barriers.
    Coureuil M, Lécuyer H, Bourdoulous S, Nassif X.
    Nat Rev Microbiol. 2017 Mar;15(3):149-159. doi: 10.1038/nrmicro.2016.178. Epub 2017 Jan 16.PMID: 28090076Review.
  • 2016

  • Structure of the Neisseria meningitidis Type IV pilus.
    Kolappan S, Coureuil M, Yu X, Nassif X, Egelman EH, Craig L.
    Nat Commun. 2016 Oct 4;7:13015. doi: 10.1038/ncomms13015.PMID: 27698424Free PMC article.
  • Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization.
    Capel E, Zomer AL, Nussbaumer T, Bole C, Izac B, Frapy E, Meyer J, Bouzinba-Ségard H, Bille E, Jamet A, Cavau A, Letourneur F, Bourdoulous S, Rattei T, Nassif X, Coureuil M.
    mBio. 2016 Aug 2;7(4):e01173-16. doi: 10.1128/mBio.01173-16.PMID: 27486197Free PMC article.
  • Experimental Evidence of Bacterial Colonization of Human Coronary Microvasculature and Myocardial Tissue during Meningococcemia.
    Bergounioux J, Coureuil M, Belli E, Ly M, Cambillau M, Goudin N, Nassif X, Join-Lambert O.
    Infect Immun. 2016 Sep 19;84(10):3017-23. doi: 10.1128/IAI.00420-16. Print 2016 Oct.PMID: 27481255Free PMC article.
  • Manipulation of host membranes by the bacterial pathogens Listeria, Francisella, Shigella and Yersinia.
    Pizarro-Cerdá J, Charbit A, Enninga J, Lafont F, Cossart P.
    Semin Cell Dev Biol. 2016 Dec;60:155-167. doi: 10.1016/j.semcdb.2016.07.019. Epub 2016 Jul 19.PMID: 27448494Free PMC article.Review.
  • Host glycosylation pathways and the unfolded protein response contribute to the infection by Francisella.
    Barel M, Harduin-Lepers A, Portier L, Slomianny MC, Charbit A.
    Cell Microbiol. 2016 Dec;18(12):1763-1781. doi: 10.1111/cmi.12614. Epub 2016 Jun 3.PMID: 27185209
  • Characterization of MDAΦ, a temperate filamentous bacteriophage of Neisseria meningitidis.
    Meyer J, Brissac T, Frapy E, Omer H, Euphrasie D, Bonavita A, Nassif X, Bille E.
    Microbiology. 2016 Feb;162(2):268-282. doi: 10.1099/mic.0.000215. Epub 2015 Nov 24.PMID: 26602366
  • 2015

  • Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients.
    Join-Lambert O, Coignard-Biehler H, Jais JP, Delage M, Guet-Revillet H, Poirée S, Duchatelet S, Jullien V, Hovnanian A, Lortholary O, Nassif X, Nassif A.
    J Antimicrob Chemother. 2016 Feb;71(2):513-20. doi: 10.1093/jac/dkv361. Epub 2015 Nov 12.PMID: 26565016
  • Remission of refractory pyoderma gangrenosum, severe acne, and hidradenitis suppurativa (PASH) syndrome using targeted antibiotic therapy in 4 patients.
    Join-Lambert O, Duchatelet S, Delage M, Miskinyte S, Coignard H, Lemarchand N, Alemy-Carreau M, Lortholary O, Nassif X, Hovnanian A, Nassif A.
    J Am Acad Dermatol. 2015 Nov;73(5 Suppl 1):S66-9. doi: 10.1016/j.jaad.2015.07.040.PMID: 26470620
  • Bacteriology of hidradenitis suppurativa/acne inversa: A review.
    Nikolakis G, Join-Lambert O, Karagiannidis I, Guet-Revillet H, Zouboulis CC, Nassif A.
    J Am Acad Dermatol. 2015 Nov;73(5 Suppl 1):S12-8. doi: 10.1016/j.jaad.2015.07.041.PMID: 26470608Review.
  • Gluconeogenesis, an essential metabolic pathway for pathogenic Francisella.
    Brissac T, Ziveri J, Ramond E, Tros F, Kock S, Dupuis M, Brillet M, Barel M, Peyriga L, Cahoreau E, Charbit A.
    Mol Microbiol. 2015 Oct;98(3):518-34. doi: 10.1111/mmi.13139. Epub 2015 Sep 10.PMID: 26192619
  • Characterization of the Maf family of polymorphic toxins in pathogenic Neisseria species.
    Jamet A, Nassif X.
    Microb Cell. 2015 Mar 2;2(3):88-90. doi: 10.15698/mic2015.03.194.PMID: 28357281Free PMC article.
  • The complex amino acid diet of Francisella in infected macrophages.
    Barel M, Ramond E, Gesbert G, Charbit A.
    Front Cell Infect Microbiol. 2015 Feb 6;5:9. doi: 10.3389/fcimb.2015.00009. eCollection 2015.PMID: 25705612Free PMC article.Review.
  • Contribution of the multiple Type I signal peptidases to the secretome of Listeria monocytogenes: deciphering their specificity for secreted exoproteins by exoproteomic analysis.
    Renier S, Chafsey I, Chambon C, Caccia N, Charbit A, Hébraud M, Desvaux M.
    J Proteomics. 2015 Mar 18;117:95-105. doi: 10.1016/j.jprot.2015.01.007. Epub 2015 Jan 28.PMID: 25637307
  • Importance of host cell arginine uptake in Francisella phagosomal escape and ribosomal protein amounts.
    Ramond E, Gesbert G, Guerrera IC, Chhuon C, Dupuis M, Rigard M, Henry T, Barel M, Charbit A.
    Mol Cell Proteomics. 2015 Apr;14(4):870-81. doi: 10.1074/mcp.M114.044552. Epub 2015 Jan 23.PMID: 25616868Free PMC article.
  • A new family of secreted toxins in pathogenic Neisseria species.
    Jamet A, Jousset AB, Euphrasie D, Mukorako P, Boucharlat A, Ducousso A, Charbit A, Nassif X.
    PLoS Pathog. 2015 Jan 8;11(1):e1004592. doi: 10.1371/journal.ppat.1004592. eCollection 2015 Jan.PMID: 25569427Free PMC article.
  • Importance of branched-chain amino acid utilization in Francisella intracellular adaptation.
    Gesbert G, Ramond E, Tros F, Dairou J, Frapy E, Barel M, Charbit A.
    Infect Immun. 2015 Jan;83(1):173-83. doi: 10.1128/IAI.02579-14. Epub 2014 Oct 20.PMID: 25332124Free PMC article.
  • 2014

  • Invasive meningococcal disease: a disease of the endothelial cells.
    Coureuil M, Bourdoulous S, Marullo S, Nassif X.
    Trends Mol Med. 2014 Oct;20(10):571-8. doi: 10.1016/j.molmed.2014.08.002. Epub 2014 Aug 29.PMID: 25178566Review.
  • Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization.
    Bernard SC, Simpson N, Join-Lambert O, Federici C, Laran-Chich MP, Maïssa N, Bouzinba-Ségard H, Morand PC, Chretien F, Taouji S, Chevet E, Janel S, Lafont F, Coureuil M, Segura A, Niedergang F, Marullo S, Couraud PO, Nassif X, Bourdoulous S.
    Nat Med. 2014 Jul;20(7):725-31. doi: 10.1038/nm.3563. Epub 2014 Jun 1.PMID: 24880614Free PMC article.
  • Permanent researcher
    Emmanuelle Bille
    -
    +33 (0)1 40 61 54 11
    Alain Charbit
    -
    +33 (0)1 40 61 54 06
    Mathieu Coureuil
    Researcher
    +33 (0)6 72 78 63 34
    Anne Jamet
    -
    Hervé Lécuyer
    Professor Researcher
    Xavier Nassif
    Professor Researcher
    +33 (0)1 40 61 54 05
    Permanent engineer
    Ravaonirina Iharilalao Dubail
    Engineer
    Marion Dupuis
    Technician
    Daniel Euphrasie
    Technician
    +33 (0)1 40 61 54 10
    Non permanent engineer
    Mélanie Montabord
    Assistant in Biological Techniques
    PhD
    Xiali Fu
    PhD Student
    Audrey Laurent
    PhD Student
    +33 (0)1 40 61 54 09
    Clémence Mouville
    PhD Student
    +33 (0)1 40 61 54 09
    Elif Uyar
    PhD Student
    Morgane Wuckelt
    PhD Student
    Student
    Clara Maubaret
    Graduate student
    Lison Reboul
    -
    Mahmoud Rifai
    -
    Address

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    Support(s)
    HRH Princess Caroline of Hanover, who through the Princess Grace Foundation, already supports medical research and anything that helps to relieve the sick children in France and around the world, has agreed to commit to our side so that our Center of Molecular medicine continues to meet the current challenges and fight diseases, and in particular the ones affecting children.

    INEM - Organigramme