Evidence map›Paper›PMID 29299844›Full record

ArticleJournal of microbiology (Seoul, Korea)2018

Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans.

Minsu Cho, Guanggan Hu, Mélissa Caza, Linda C Horianopoulos, James W Kronstad, Won Hee Jung

Open access · greenAbstract read
In one paragraph

Article in Journal of microbiology (Seoul, Korea), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Fungal-Metal Interactions: A Review of Toxicity and Homeostasis.Journal of fungi (Basel, Switzerland) · 2021
    Review
  7. Zinc at the Host-Fungus Interface: How to Uptake the Metal?Journal of fungi (Basel, Switzerland) · 2020
    Review
  8. Transcription factors and transporters in zinc homeostasis: lessons learned from fungi.Critical reviews in biochemistry and molecular biology · 2020
    Review
  9. Article
  10. Article
  11. 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.

Minsu ChoDepartment of Systems Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea.
Guanggan HuMichael Smith Laboratories, University of British Columbia, Vancouver, B.C., V6T 1Z4, Canada.
Mélissa CazaMichael Smith Laboratories, University of British Columbia, Vancouver, B.C., V6T 1Z4, Canada.
Linda C HorianopoulosMichael Smith Laboratories, University of British Columbia, Vancouver, B.C., V6T 1Z4, Canada.
James W KronstadMichael Smith Laboratories, University of British Columbia, Vancouver, B.C., V6T 1Z4, Canada.
Won Hee JungDepartment of Systems Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea. whjung@cau.ac.kr.
Canada's Michael Smith Genome Sciences Centre · CAChung-Ang University · KRUniversity of British Columbia · CA

Funding

Comparative and functional genomics of C. neoformansR01AI053721 · NIAID · UNIVERSITY OF BRITISH COLUMBIA · PI KRONSTAD, JAMES W · 2003 to 2024
$5.4M
NIAID NIH HHS R01 AI053721
6 · The paper itself

Abstract

Zinc is an important transition metal in all living organisms and is required for numerous biological processes. However, excess zinc can also be toxic to cells and cause cellular stress. In the model fungus Saccharomyces cerevisiae, a vacuolar zinc transporter, Zrc1, plays important roles in the storage and detoxification of excess intracellular zinc to protect the cell. In this study, we identified an ortholog of the S. cerevisiae ZRC1 gene in the human fungal pathogen Cryptococcus neoformans. Zrc1 was localized in the vacuolar membrane in C. neoformans, and a mutant lacking ZRC1 showed significant growth defects under high-zinc conditions. These results suggested a role for Zrc1 in zinc detoxification. However, contrary to our expectation, the expression of Zrc1 was induced in cells grown in zinc-limited conditions and decreased upon the addition of zinc. These expression patterns were similar to those of Zip1, the high-affinity zinc transporter in the plasma membrane of C. neoformans. Furthermore, we used the zrc1 mutant in a murine model of cryptococcosis to examine whether a mammalian host could inhibit the survival of C. neoformans using zinc toxicity. We found that the mutant showed no difference in virulence compared with the wildtype strain. This result suggests that Zrc1-mediated zinc detoxification is not required for the virulence of C. neoformans, and imply that zinc toxicity may not be an important aspect of the host immune response to the fungus.

Indexed as

Amino Acid SequenceAnimalsBacterial ProteinsCation Transport ProteinsCryptococcosisCryptococcus neoformansFemaleHumansMiceMice, Inbred BALB CMolecular Sequence DataSequence AlignmentVacuolesVirulenceZincBacterial ProteinsCation Transport ProteinsZincCryptococcus neoformansvacuolevirulencezincZrc1

Identifiers

PMID29299844
PMCPMC7552933
OpenAlexW2782271122

What OpenQuestion holds

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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.