Evidence map›Paper›PMID 21249145›Full record

ArticlePloS one2011

Cryptococcus gattii virulence composite: candidate genes revealed by microarray analysis of high and less virulent Vancouver island outbreak strains.

Popchai Ngamskulrungroj, Jennifer Price, Tania Sorrell, John R Perfect, Wieland Meyer

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
  2. Review
  3. Genotyping Analysis ofJournal of fungi (Basel, Switzerland) · 2023
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  4. Gene, virulence and related regulatory mechanisms inActa biochimica et biophysica Sinica · 2022
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Macrolides Inhibit Capsule Formation of Highly VirulentAntimicrobial agents and chemotherapy · 2019
    Article
  12. Article
  13. Article
  14. Review
  15. Cryptococcosis today: It is not all about HIV infection.Current clinical microbiology reports · 2017
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

5 authors at 4 institutions in 3 countries.

Popchai NgamskulrungrojMolecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School-Westmead, Westmead Millennium Institute, Sydney Emerging Infections and Biosecurity Institute, The University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia.
Jennifer Price
Tania Sorrell
John R Perfect
Wieland Meyer
The University of Sydney · AUDuke Medical Center · USMahidol University · THWestmead Institute · AU

Funding

Pathobiology of C. neoformans in the Central Nervous SystemR01AI073896 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2008 to 2018
$4.4M
GENTIC &MOLECULAR BIOLOGY OF VIRULENCE IN C. NEOFORMANSR01AI028388 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1991 to 2004
$1.9M
Genetic molecular biology of virulence in C. neoformansR56AI028388 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2006 to 2006
$389k
NIAID NIH HHS AI28388NIAID NIH HHS AI73896NIAID NIH HHS R01 AI028388NIAID NIH HHS R01 AI073896NIAID NIH HHS R56 AI028388
6 · The paper itself

Abstract

Human and animal cryptococcosis due to an unusual molecular type of Cryptococcus gattii (VGII) emerged recently on Vancouver Island, Canada. Unlike C. neoformans, C. gattii causes disease mainly in immunocompetent hosts, despite producing a similar suite of virulence determinants. To investigate a potential relationship between the regulation of expression of a virulence gene composite and virulence, we took advantage of two subtypes of VGII (a and b), one highly virulent (R265) and one less virulent (R272), that were identified from the Vancouver outbreak. By expression microarray analysis, 202 genes showed at least a 2-fold difference in expression with 108 being up- and 94 being down-regulated in strain R265 compared with strain R272. Specifically, expression levels of genes encoding putative virulence factors (e.g. LAC1, LAC2, CAS3 and MPK1) and genes encoding proteins involved in cell wall assembly, carbohydrate and lipid metabolism were increased in strain R265, whereas genes involved in the regulation of mitosis and ergosterol biosynthesis were suppressed. In vitro phenotypic studies and transcription analysis confirmed the microarray results. Gene disruption of LAC1 and MPK1 revealed defects in melanin synthesis and cell wall integrity, respectively, where CAS3 was not essential for capsule production. Moreover, MPK1 also controls melanin and capsule production and causes a severe attenuation of the virulence in a murine inhalational model. Overall, this study provides the basis for further genetic studies to characterize the differences in the virulence composite of strains with minor evolutionary divergences in gene expression in the primary pathogen C. gattii, that have led to a major invasive fungal infection outbreak.

Indexed as

Disease OutbreaksGene Expression ProfilingGene Expression Regulation, FungalCanadaCryptococcosisCryptococcus gattiiEvolution, MolecularGeographyHumansOligonucleotide Array Sequence AnalysisSpecies SpecificityVirulence

Identifiers

PMID21249145
PMCPMC3020960
OpenAlexW2108051940

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.