Peripheral blood vessels are a niche for blood-borne meningococci. 2017

Elena Capel, and Jean-Philippe Barnier, and Aldert L Zomer, and Christine Bole-Feysot, and Thomas Nussbaumer, and Anne Jamet, and Hervé Lécuyer, and Daniel Euphrasie, and Zoé Virion, and Eric Frapy, and Philippe Pélissier, and Olivier Join-Lambert, and Thomas Rattei, and Sandrine Bourdoulous, and Xavier Nassif, and Mathieu Coureuil
a Institut Necker Enfants-Malades, INSERM U1151, Equipe 11 , Paris , France.

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.

UI MeSH Term Description Entries
D008589 Meningococcal Infections Infections with bacteria of the species NEISSERIA MENINGITIDIS. Meningococcal Septicemia,Infections, Meningococcal,Meningococcal Disease,Infection, Meningococcal,Meningococcal Diseases,Meningococcal Infection,Septicemia, Meningococcal
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009345 Neisseria meningitidis A species of gram-negative, aerobic BACTERIA. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the NASOPHARYNX. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis (MENINGITIS, MENINGOCOCCAL). It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being A, B, C, Y, and W-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Diplokokkus intracellularis meningitidis,Meningococcus,Micrococcus intracellularis,Micrococcus meningitidis,Micrococcus meningitidis cerebrospinalis,Neisseria weichselbaumii
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001422 Bacterial Adhesion Physicochemical property of fimbriated (FIMBRIAE, BACTERIAL) and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity. Adhesion, Bacterial,Adhesions, Bacterial,Bacterial Adhesions
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D016470 Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Bacteremias
D016513 Mice, SCID Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice. SCID Mice,SCID-hu Mice,Severe Combined Immunodeficient Mice,Immunodeficient Mice, Severe Combined,Mouse, SCID,Mouse, SCID-hu,Mice, SCID-hu,Mouse, SCID hu,SCID Mouse,SCID hu Mice,SCID-hu Mouse

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