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Mycobacterium tuberculosis Invasion and Traversal across an In Vitro Human Blood-Brain Barrier as a Pathogenic Mechanism for Central Nervous System Tuberculosis
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Mycobacterium tuberculosis Invasion and Traversal across an In Vitro Human Blood-Brain Barrier as a Pathogenic Mechanism for Central Nervous System Tuberculosis
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Mycobacterium tuberculosis Invasion and Traversal across an In Vitro Human Blood-Brain Barrier as a Pathogenic Mechanism for Central Nervous System Tuberculosis
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Journal Article
Mycobacterium tuberculosis Invasion and Traversal across an In Vitro Human Blood-Brain Barrier as a Pathogenic Mechanism for Central Nervous System Tuberculosis
2006
Overview
BackgroundCentral nervous system (CNS) tuberculosis is a serious, often fatal disease that disproportionately affects young children. It is thought to develop when Mycobacterium tuberculosis breaches the blood-brain barrier (BBB), which is composed of tightly apposed brain microvascular endothelial cells. However, the mechanism(s) involved in this process are poorly understood Methods To better understand these processes, we developed an in vitro model of M. tuberculosis BBB infection using primary human brain microvascular endothelial cells ResultsM. tuberculosis was found to both invade and traverse the model BBB significantly more than did M. smegmatis (a nonpathogenic mycobacterium). Invasion by M. tuberculosis across the BBB required host-cell actin cytoskeletal rearrangements. By microarray expression profiling, we found 33 M. tuberculosis genes to be highly up-regulated during the early stages of invasion of the BBB by M. tuberculosis; 18 of them belong to a previously described in vivo–expressed genomic island (Rv0960–Rv1001). Defined M. tuberculosis isogenic transposon mutants for the up-regulated genes Rv0980c, Rv0987, Rv0989c and Rv1801 were found to be deficient in their ability to invade the BBB model ConclusionsWe developed an in vitro model of M. tuberculosis BBB infection and identified M. tuberculosis genes that may be involved in CNS invasion
Publisher
The University of Chicago Press,University of Chicago Press,Oxford University Press
Subject
/ Bacteria
/ Biological and medical sciences
/ Blood-Brain Barrier - microbiology
/ Brain
/ Central nervous system tuberculosis
/ Endothelium, Vascular - cytology
/ Endothelium, Vascular - metabolism
/ Endothelium, Vascular - microbiology
/ Fundamental and applied biological sciences. Psychology
/ Humans
/ Mutation
/ Mycobacterium tuberculosis - genetics
/ Mycobacterium tuberculosis - pathogenicity
/ Mycobacterium tuberculosis - ultrastructure
/ Tuberculosis and atypical mycobacterial infections
/ Tuberculosis, Central Nervous System - genetics
/ Tuberculosis, Central Nervous System - microbiology
