Evidence map›Paper›PMID 22897198›Full record

ArticleMolecular microbiology2012

Deletion of mitochondrial associated ubiquitin fold modifier protein Ufm1 in Leishmania donovani results in loss of β-oxidation of fatty acids and blocks cell division in the amastigote stage.

Sreenivas Gannavaram, Patricia S Connelly, Mathew P Daniels, Robert Duncan, Poonam Salotra, Hira L Nakhasi

Open access · greenAbstract read
In one paragraph

Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

26 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Three types ofFrontiers in cellular and infection microbiology · 2022
    Article
  5. A description of novel variants and review of phenotypic spectrum inCold Spring Harbor molecular case studies · 2021
    Article
  6. Article
  7. Article
  8. TheGenes · 2020
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. UFMylation: A Unique & Fashionable Modification for Life.Genomics, proteomics & bioinformatics · 2016
    Review
  18. Article
  19. Review
  20. The ufm1 cascade.Cells · 2014
    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

6 authors at 3 institutions in 2 countries.

Sreenivas GannavaramLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20892, USA.
Patricia S Connelly
Mathew P Daniels
Robert Duncan
Poonam Salotra
Hira L Nakhasi
Center for Biologics Evaluation and Research · USNational Heart Lung and Blood Institute · USNational Institute of Pathology · IN

Funding

Electron Microscopy CoreZICHL005906 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SYED, ZULFEQHAR · 2009 to 2025
$12.9M
Intramural NIH HHS ZIC HL005906
6 · The paper itself

Abstract

Recently, we described the existence of the ubiquitin fold modifier 1 (Ufm1) and its conjugation pathway in Leishmania donovani. We demonstrated the conjugation of Ufm1 to proteins such as mitochondrial trifunctional protein (MTP) that catalyses β-oxidation of fatty acids in L. donovani. To elucidate the biological roles of the Ufm1-mediated modifications, we made an L. donovani Ufm1 null mutant (Ufm1(-/-)). Loss of Ufm1 and consequently absence of Ufm1 conjugation with MTP resulted in diminished acetyl-CoA, the end-product of the β-oxidation in the Ufm1(-/-) amastigote stage. The Ufm1(-/-) mutants showed reduced survival in the amastigote stage in vitro and ex vivo in human macrophages. This survival was restored by re-expression of wild-type Ufm1 with concomitant induction of acetyl-CoA but not by re-expressing the non-conjugatable Ufm1, indicating the essential nature of Ufm1 conjugation and β-oxidation. Both cell cycle analysis and ultrastructural studies of Ufm1(-/-) parasites confirmed the role of Ufm1 in amastigote growth. The defect in vitro growth of amastigotes in human macrophages was further substantiated by reduced survival. Therefore, these studies suggest the importance of Ufm1 in Leishmania pathogenesis with larger impact on other organisms and further provide an opportunity to test Ufm1(-/-) parasites as drug and vaccine targets.

Indexed as

Cell DivisionGene DeletionCell SurvivalFatty AcidsGenetic Complementation TestHumansLeishmania donovaniMacrophagesOxidation-ReductionProtozoan ProteinsUbiquitinFatty AcidsProtozoan ProteinsUbiquitin

Identifiers

PMID22897198
PMCPMC4249706
OpenAlexW2171637519

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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.