Abstract:
:Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU) disease, is unique amongst human pathogens in its capacity to produce a lipid toxin called mycolactone. While previous studies have demonstrated that bacterially-released mycolactone diffuses beyond infection foci, the spatiotemporal distribution of mycolactone remained largely unknown. Here, we used the zebrafish model to provide the first global kinetic analysis of mycolactone's diffusion in vivo, and multicellular co-culture systems to address the critical question of the toxin's access to the brain. Zebrafish larvae were injected with a fluorescent-derivative of mycolactone to visualize the in vivo diffusion of the toxin from the peripheral circulation. A rapid, body-wide distribution of mycolactone was observed, with selective accumulation in tissues near the injection site and brain, together with an important excretion through the gastro-intestinal tract. Our conclusion that mycolactone reached the central nervous system was reinforced by an in cellulo model of human blood brain barrier and a mouse model of M. ulcerans-infection. Here we show that mycolactone has a broad but heterogenous profile of distribution in vivo. Our investigations in vitro and in vivo support the view that a fraction of bacterially-produced mycolactone gains access to the central nervous system. The relative persistence of mycolactone in the bloodstream suggests that assays of circulating mycolactone are relevant for BU disease monitoring and treatment optimization.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Colucci-Guyon E,Rifflet A,Saint-Auret S,da Costa A,Boucontet L,Laval T,Prehaud C,Blanchard N,Levraud JP,Boneca IG,Demangel C,Guenin-Macé Ldoi
10.1371/journal.pntd.0008878subject
Has Abstractpub_date
2020-12-02 00:00:00pages
e0008878issue
12eissn
1935-2727issn
1935-2735pii
PNTD-D-20-00990journal_volume
14pub_type
杂志文章abstract:BACKGROUND:Monitoring of insect vector populations with respect to their susceptibility to one or more insecticides is a crucial element of the strategies used for the control of arthropod-borne diseases. This management task can nowadays be achieved more efficiently when assisted by IT (Information Technology) tools, ...
journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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