Peripheral blood vessels are a niche for blood-borne meningococci

Virulence
Elena CapelMathieu Coureuil

Abstract

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 sep...Continue Reading

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Citations

Jun 6, 2019·Cellular Microbiology·Mathieu CoureuilXavier Nassif
Mar 19, 2020·Cellular Microbiology·Isabel Dos Santos SouzaSandrine Bourdoulous
Mar 27, 2019·Nature Microbiology·Kevin DenisSandrine Bourdoulous
Nov 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jean-Philippe BarnierMathieu Coureuil

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Methods Mentioned

BETA
biopsies
PCR
Illumina sequencing

Software Mentioned

fastx
EdgeR
ESSENTIAL
ESSENTIALS
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CD

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