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Phthiocerol dimycocerosates promote access to the cytosol and intracellular burden of Mycobacterium tuberculosis in lymphatic endothelial cells

Overview of attention for article published in BMC Biology, January 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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20 tweeters

Citations

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12 Dimensions

Readers on

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24 Mendeley
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Title
Phthiocerol dimycocerosates promote access to the cytosol and intracellular burden of Mycobacterium tuberculosis in lymphatic endothelial cells
Published in
BMC Biology, January 2018
DOI 10.1186/s12915-017-0471-6
Pubmed ID
Authors

Thomas R. Lerner, Christophe J. Queval, Antony Fearns, Urska Repnik, Gareth Griffiths, Maximiliano G. Gutierrez

Abstract

Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as macrophages and dendritic cells, are the primary hosts for Mtb after infection and previous studies have shown multiple roles for PDIM in supporting Mtb in these cells. However, Mtb can infect other cell types. We previously showed that Mtb efficiently replicates in human lymphatic endothelial cells (hLECs) and that the hLEC cytosol acts as a reservoir for Mtb in humans. Here, we examined the role of PDIM in Mtb translocation to the cytosol in hLECs. Analysis of a Mtb mutant unable to produce PDIM showed less co-localisation of bacteria with the membrane damage marker Galectin-8 (Gal8), indicating that PDIM strongly contribute to phagosomal membrane damage. Lack of this Mtb lipid also leads to a reduction in the proportion of Mtb co-localising with markers of macroautophagic removal of intracellular bacteria (xenophagy) such as ubiquitin, p62 and NDP52. hLEC imaging with transmission electron microscopy shows that Mtb mutants lacking PDIM are much less frequently localised in the cytosol, leading to a lower intracellular burden. PDIM is needed for the disruption of the phagosome membrane in hLEC, helping Mtb avoid the hydrolytic phagolysosomal milieu. It facilitates the translocation of Mtb into the cytosol, and the decreased intracellular burden of Mtb lacking PDIM indicates that the cytosol is the preferred replicative niche for Mtb in these cells. We hypothesise that pharmacological targeting of PDIM synthesis in Mtb would reduce the formation of a lymphatic reservoir of Mtb in humans.

Twitter Demographics

The data shown below were collected from the profiles of 20 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 42%
Student > Master 5 21%
Unspecified 3 13%
Researcher 2 8%
Professor > Associate Professor 2 8%
Other 2 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 25%
Biochemistry, Genetics and Molecular Biology 6 25%
Unspecified 5 21%
Immunology and Microbiology 3 13%
Medicine and Dentistry 3 13%
Other 1 4%

Attention Score in Context

This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 May 2019.
All research outputs
#1,443,315
of 13,406,972 outputs
Outputs from BMC Biology
#474
of 1,185 outputs
Outputs of similar age
#61,225
of 384,552 outputs
Outputs of similar age from BMC Biology
#69
of 128 outputs
Altmetric has tracked 13,406,972 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,185 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.7. This one has gotten more attention than average, scoring higher than 59% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 384,552 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 128 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.