Evidence map›Paper›PMID 29904094›Full record

ArticleScientific reports2018

Parasite motility is critical for virulence of African trypanosomes.

Michelle M Shimogawa, Sunayan S Ray, Neville Kisalu, Yibo Zhang, Quanjie Geng, Aydogan Ozcan, Kent L Hill

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

37 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Article
  3. Virulence · 2025
    Article
  4. CryoEM structure of thebioRxiv : the preprint server for biology · 2025
    Article
  5. Modelling motility of Trypanosoma brucei.PLoS computational biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. FAP20 is required for flagellum assembly inMolecular biology of the cell · 2024
    Article
  10. FAP20 is required for flagellum assembly inbioRxiv : the preprint server for biology · 2024
    Article
  11. Propulsive cell entry diverts pathogens from immune degradation by remodeling the phagocytic synapse.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Transmigration ofiScience · 2022
    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

7 authors at 2 institutions in 1 country.

Michelle M ShimogawaDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
Sunayan S RayDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
Neville KisaluDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
Yibo ZhangElectrical and Computer Engineering Department, University of California, Los Angeles, CA, 90095, USA.ORCID 0000-0002-5636-7085
Quanjie GengElectrical and Computer Engineering Department, University of California, Los Angeles, CA, 90095, USA.
Aydogan OzcanElectrical and Computer Engineering Department, University of California, Los Angeles, CA, 90095, USA.ORCID 0000-0002-0717-683X
Kent L HillDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA. kenthill@microbio.ucla.edu.
University of California, Los Angeles · USCalifornia NanoSystems Institute · US

Funding

Biochemical and Functional Analysis of TrypaninR01AI052348 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HILL, KENT L · 2002 to 2023
$7.4M
Biochemical and Functional Analysis of TrypaninR56AI052348 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HILL, KENT L · 2007 to 2007
$374k
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI052348NIAID NIH HHS R56 AI052348
6 · The paper itself

Abstract

African trypanosomes, Trypanosoma brucei spp., are lethal pathogens that cause substantial human suffering and limit economic development in some of the world's most impoverished regions. The name Trypanosoma ("auger cell") derives from the parasite's distinctive motility, which is driven by a single flagellum. However, despite decades of study, a requirement for trypanosome motility in mammalian host infection has not been established. LC1 is a conserved dynein subunit required for flagellar motility. Prior studies with a conditional RNAi-based LC1 mutant, RNAi-K/R, revealed that parasites with defective motility could infect mice. However, RNAi-K/R retained residual expression of wild-type LC1 and residual motility, thus precluding definitive interpretation. To overcome these limitations, here we generate constitutive mutants in which both LC1 alleles are replaced with mutant versions. These double knock-in mutants show reduced motility compared to RNAi-K/R and are viable in culture, but are unable to maintain bloodstream infection in mice. The virulence defect is independent of infection route but dependent on an intact host immune system. By comparing different mutants, we also reveal a critical dependence on the LC1 N-terminus for motility and virulence. Our findings demonstrate that trypanosome motility is critical for establishment and maintenance of bloodstream infection, implicating dynein-dependent flagellar motility as a potential drug target.

Indexed as

FlagellaMutationTrypanosoma brucei bruceiTrypanosomiasis, AfricanAnimalsCattleFemaleMiceMice, Inbred BALB C

Identifiers

PMID29904094
PMCPMC6002391
OpenAlexW2805961072

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.