Evidence map›Paper›PMID 34432856›Full record

ArticlePLoS pathogens2021

Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.

Stephen J Fairweather, Esther Rajendran, Martin Blume, Kiran Javed, Birte Steinhöfel, Malcolm J McConville, Kiaran Kirk, Stefan Bröer, Giel G van Dooren

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

19 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  3. A two-membrane gateway for monocarboxylates couples host glycolysis tobioRxiv : the preprint server for biology · 2026
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  6. Review
  7. PfApiAT2 is a proline transporter essential for the transmission ofbioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. The intersection of hostMicrobiology and molecular biology reviews : MMBR · 2024
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. 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

9 authors at 2 institutions in 2 countries.

Stephen J FairweatherResearch School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.ORCID 0000-0003-1530-7876
Esther RajendranResearch School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.ORCID 0000-0002-8036-9531
Martin BlumeDepartment of Biochemistry and Molecular Biology and the Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria, Australia.ORCID 0000-0002-6894-3000
Kiran JavedResearch School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
Birte SteinhöfelResearch School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.ORCID 0000-0003-0927-4836
Malcolm J McConvilleDepartment of Biochemistry and Molecular Biology and the Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria, Australia.ORCID 0000-0002-7107-7887
Kiaran KirkResearch School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.ORCID 0000-0002-5613-2622
Stefan BröerResearch School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.ORCID 0000-0002-8040-1634
Giel G van DoorenResearch School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.ORCID 0000-0003-2455-9821
Australian National University · AUThe University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intracellular parasites of the phylum Apicomplexa are dependent on the scavenging of essential amino acids from their hosts. We previously identified a large family of apicomplexan-specific plasma membrane-localized amino acid transporters, the ApiATs, and showed that the Toxoplasma gondii transporter TgApiAT1 functions in the selective uptake of arginine. TgApiAT1 is essential for parasite virulence, but dispensable for parasite growth in medium containing high concentrations of arginine, indicating the presence of at least one other arginine transporter. Here we identify TgApiAT6-1 as the second arginine transporter. Using a combination of parasite assays and heterologous characterisation of TgApiAT6-1 in Xenopus laevis oocytes, we demonstrate that TgApiAT6-1 is a general cationic amino acid transporter that mediates both the high-affinity uptake of lysine and the low-affinity uptake of arginine. TgApiAT6-1 is the primary lysine transporter in the disease-causing tachyzoite stage of T. gondii and is essential for parasite proliferation. We demonstrate that the uptake of cationic amino acids by TgApiAT6-1 is 'trans-stimulated' by cationic and neutral amino acids and is likely promoted by an inwardly negative membrane potential. These findings demonstrate that T. gondii has evolved overlapping transport mechanisms for the uptake of essential cationic amino acids, and we draw together our findings into a comprehensive model that highlights the finely-tuned, regulated processes that mediate cationic amino acid scavenging by these intracellular parasites.

Indexed as

Amino Acids, EssentialAmino Acid Transport Systems, BasicAnimalsArginineBiological TransportFibroblastsHumansLysineOocytesProtozoan ProteinsToxoplasmaToxoplasmosisXenopus laevisAmino Acids, EssentialAmino Acid Transport Systems, BasicArginineLysineProtozoan Proteins

Identifiers

PMID34432856
PMCPMC8423306
OpenAlexW3174879961

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.