Evidence map›Paper›PMID 23550133›Full record

ArticleG3 (Bethesda, Md.)2013

Comparative Genomics of Serial Isolates of Cryptococcus neoformans Reveals Gene Associated With Carbon Utilization and Virulence.

Kate L Ormerod, Carl A Morrow, Eve W L Chow, I Russel Lee, Samantha D M Arras, Horst Joachim Schirra, Gary M Cox, Bettina C Fries, James A Fraser

Open access · goldAbstract read
In one paragraph

Article in G3 (Bethesda, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

50 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  9. Article
  10. Adaptative Divergence ofJournal of fungi (Basel, Switzerland) · 2025
    Article
  11. Effects of COCurrent opinion in microbiology · 2024
    Review
  12. Microevolution during Chronic Infection May LeadDermatology research and practice · 2024
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Impact of pathogen genetics on clinical phenotypes in a population ofbioRxiv : the preprint server for biology · 2023
    Article
  19. Importance of Clinical Isolates inJournal of fungi (Basel, Switzerland) · 2023
    Review
  20. Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogenProceedings of the National Academy of Sciences of the United States of America · 2023
    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 4 institutions in 2 countries.

Kate L OrmerodAustralian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072 Australia.
Carl A MorrowAustralian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072 Australia.
Eve W L ChowAustralian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072 Australia.
I Russel LeeAustralian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072 Australia.
Samantha D M ArrasAustralian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072 Australia.
Horst Joachim SchirraSchool of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072 Australia.
Gary M CoxDepartment of Medicine, Mycology Research Unit, Duke University, Durham, North Carolina 27710.
Bettina C FriesDepartment of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York 10461.
James A FraserAustralian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072 Australia jafraser@uq.edu.au.
University of Queensland · AUAlbert Einstein College of Medicine · USDuke University · USNational Imaging Facility · AU

Funding

response to phenotypic switch variants to C. neoformansR01AI059681 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI FRIES, BETTINA · 2004 to 2014
$3.6M
NIAID NIH HHS R01 AI059681
6 · The paper itself

Abstract

The opportunistic fungal pathogen Cryptococcus neoformans is a leading cause of mortality among the human immunodeficiency virus/acquired immunodeficiency syndrome population and is known for frequently causing life-threatening relapses. To investigate the potential contribution of in-host microevolution to persistence and relapse, we have analyzed two serial isolates obtained from a patient with acquired immunodeficiency syndrome who suffered an initial and relapse episode of cryptococcal meningoencephalitis. Despite being identical by multilocus sequence typing, the isolates differ phenotypically, exhibiting changes in key virulence factors, nutrient acquisition, metabolic profiles, and the ability to disseminate in an animal model. Whole-genome sequencing uncovered a clonal relationship, with only a few unique differences. Of these, two key changes are expected to explain the phenotypic differences observed in the relapse isolate: loss of a predicted AT-rich interaction domain protein and changes in copy number of the left and right arms of chromosome 12. Gene deletion of the predicted transcriptional regulator produced changes in melanin, capsule, carbon source use, and dissemination in the host, consistent with the phenotype of the relapse isolate. In addition, the deletion mutant displayed altered virulence in the murine model. The observed differences suggest the relapse isolate evolved subsequent to penetration of the central nervous system and may have gained dominance following the administration of antifungal therapy. These data reveal the first molecular insights into how the Cryptococcus neoformans genome changes during infection of humans and the manner in which microevolution progresses in this deadly fungal pathogen.

Indexed as

cryptococcosisfungal pathogenesismicroevolutionrelapse

Identifiers

PMID23550133
PMCPMC3618354
OpenAlexW2058779017

What OpenQuestion holds

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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.