Evidence map›Paper›PMID 25956932›Full record

ArticleBMC genomics2015

Lipid metabolism and Type VII secretion systems dominate the genome scale virulence profile of Mycobacterium tuberculosis in human dendritic cells.

Tom A Mendum, Huihai Wu, Andrzej M Kierzek, Graham R Stewart

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. The Lack of the TetR-Like Repressor GeneFrontiers in cellular and infection microbiology · 2022
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2018
    Review
  11. Modeling the Metabolic State ofFrontiers in cellular and infection microbiology · 2018
    Article
  12. Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. MUFINS: multi-formalism interaction network simulator.NPJ systems biology and applications · 2016
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Tom A MendumDepartment of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK. t.mendum@surrey.ac.uk.
Huihai WuDepartment of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK. h.wu@surrey.ac.uk.
Andrzej M KierzekDepartment of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK. a.kierzek@surrey.ac.uk.
Graham R StewartDepartment of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK. g.stewart@surrey.ac.uk.
University of Surrey · GB

Funding

Biotechnology and Biological Sciences Research Council BB/I00453X/1Medical Research Council G0900740Medical Research Council MR/K001744/1Wellcome Trust WT090242MA
6 · The paper itself

Abstract

backgroundMycobacterium tuberculosis continues to kill more people than any other bacterium. Although its archetypal host cell is the macrophage, it also enters, and survives within, dendritic cells (DCs). By modulating the behaviour of the DC, M. tuberculosis is able to manipulate the host's immune response and establish an infection. To identify the M. tuberculosis genes required for survival within DCs we infected primary human DCs with an M. tuberculosis transposon library and identified mutations with a reduced ability to survive.

resultsParallel sequencing of the transposon inserts of the surviving mutants identified a large number of genes as being required for optimal intracellular fitness in DCs. Loci whose mutation attenuated intracellular survival included those involved in synthesising cell wall lipids, not only the well-established virulence factors, pDIM and cord factor, but also sulfolipids and PGL, which have not previously been identified as having a direct virulence role in cells. Other attenuated loci included the secretion systems ESX-1, ESX-2 and ESX-4, alongside many PPE genes, implicating a role for ESX-5. In contrast the canonical ESAT-6 family of ESX substrates did not have intra-DC fitness costs suggesting an alternative ESX-1 associated virulence mechanism. With the aid of a gene-nutrient interaction model, metabolic processes such as cholesterol side chain catabolism, nitrate reductase and cysteine-methionine metabolism were also identified as important for survival in DCs.

conclusionWe conclude that many of the virulence factors required for survival in DC are shared with macrophages, but that survival in DCs also requires several additional functions, such as cysteine-methionine metabolism, PGLs, sulfolipids, ESX systems and PPE genes.

Indexed as

GenomicsCell WallCholesterolDendritic CellsDNA Transposable ElementsGenome, BacterialHumansLipid MetabolismMacrophagesMutationMycobacterium tuberculosisOxidative StressPhagosomesReactive Nitrogen SpeciesType VII Secretion SystemsVirulenceCholesterolDNA Transposable ElementsReactive Nitrogen SpeciesType VII Secretion Systems

Identifiers

PMID25956932
PMCPMC4425887
OpenAlexW1598308220

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.