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

Neisseria meningitidisis the causative agent of cerebrospinal meningitis and that of a rapidly progressing fatal septic shock known aspurpura 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 inN. meningitidisassociated pathogenesis. In this work, using a humanized model of SCID mice allowing the study of bacterial adhesion to human cells in anin vivocontext 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 forN. 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. [ABSTRACT FROM AUTHOR]