1. Peripheral blood vessels are a niche for blood-borne meningococci
- Author
-
Capel, Elena, Barnier, Jean-Philippe, Zomer, Aldert L, Bole-Feysot, Christine, Nussbaumer, Thomas, Jamet, Anne, Lécuyer, Hervé, Euphrasie, Daniel, Virion, Zoé, Frapy, Eric, Pélissier, Philippe, Join-Lambert, Olivier, Rattei, Thomas, Bourdoulous, Sandrine, Nassif, Xavier, Coureuil, Mathieu, dI&I I&I-4, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Utrecht University [Utrecht], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Vienna [Vienna], Centre hospitalier Saint-Joseph [Paris], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Coureuil, Mathieu, and dI&I I&I-4
- Subjects
0301 basic medicine ,Microbiology (medical) ,Immunology ,Virulence ,Context (language use) ,Bacteremia ,Mice, SCID ,Biology ,Neisseria meningitidis ,medicine.disease_cause ,purpura fulminans ,Microbiology ,Bacterial Adhesion ,Sepsis ,03 medical and health sciences ,nutritional virulence ,Mice ,Bacterial Proteins ,In vivo ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,medicine ,Animals ,Humans ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,Mice, Inbred BALB C ,Septic shock ,host cell interaction ,Tn-seq ,medicine.disease ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Meningococcal Infections ,030104 developmental biology ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Editorial ,Microvessels ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Parasitology ,Female ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Purpura fulminans - Abstract
International audience; Neisseria meningitidis is the causative agent of cerebrospinal meningitis and that of a rapidly progressing fatal septic shock known as purpura fulminans. Meningococcemia is characterized by bacterial adhesion to human endothelial cells of the microvessels. Host specificity has hampered studies on the role of blood vessels colonization in N. meningitidis associated pathogenesis. In this work, using a humanized model of SCID mice allowing the study of bacterial adhesion to human cells in an in vivo context we demonstrate that meningococcal colonization of human blood vessels is a prerequisite to the establishment of sepsis and lethality. To identify the molecular pathways involved in bacterial virulence, we performed transposon insertion site sequencing (Tn-seq) in vivo. Our results demonstrate that 36% of the genes that are important for growth in the blood of mice are dispensable when bacteria colonize human blood vessels, suggesting that human endothelial cells lining the blood vessels are feeding niches for N. meningitidis in vivo. Altogether, our work proposes a new paradigm for meningococcal virulence in which colonization of blood vessels is associated with metabolic adaptation and sustained bacteremia responsible for sepsis and subsequent lethality.
- Published
- 2017