Evidence map›Paper›PMID 22952924›Full record

ArticlePloS one2012

Calcineurin is required for pseudohyphal growth, virulence, and drug resistance in Candida lusitaniae.

Jing Zhang, Fitz Gerald S Silao, Ursela G Bigol, Alice Alma C Bungay, Marilou G Nicolas, Joseph Heitman, Ying-Lien Chen

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. 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
3.5field-weighted citation impact, top 7% 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, 58 citations in OpenAlex.

  1. Article
  2. First Case of Cutaneous Coinfection withDiagnostics (Basel, Switzerland) · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Frontiers in microbiology · 2023
    Article
  9. Review
  10. CaJournal of fungi (Basel, Switzerland) · 2022
    Article
  11. Article
  12. Article
  13. Infection and drug resistance · 2022
    Review
  14. Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis.Frontiers in cellular and infection microbiology · 2021
    Review
  15. Combination Therapy to Treat Fungal Biofilm-Based Infections.International journal of molecular sciences · 2020
    Review
  16. Review
  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

7 authors at 3 institutions in 2 countries.

Jing ZhangDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA.
Fitz Gerald S Silao
Ursela G Bigol
Alice Alma C Bungay
Marilou G Nicolas
Joseph Heitman
Ying-Lien Chen
Duke University · USUniversity of Perpetual Help System DALTA · PHUniversity of the Philippines Manila · PH

Funding

Social and Behavioral Sciences CoreP30AI064518 · NIAID · DUKE UNIVERSITY · PI Nwora Lance Okeke · 2005 to 2026
$50.5M
Novel Antifungal Therapeutic ApproachesR01AI050438 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 2001 to 2012
$3.3M
NIAID NIH HHS 2P30 AI064518-06NIAID NIH HHS AI50438NIAID NIH HHS P30 AI064518NIAID NIH HHS R01 AI050438
6 · The paper itself

Abstract

Candida lusitaniae is an emerging fungal pathogen that infects immunocompromised patients including HIV/AIDS, cancer, and neonatal pediatric patients. Though less prevalent than other Candida species, C. lusitaniae is unique in its ability to develop resistance to amphotericin B. We investigated the role of the calcium-activated protein phosphatase calcineurin in several virulence attributes of C. lusitaniae including pseudohyphal growth, serum survival, and growth at 37°C. We found that calcineurin and Crz1, a C. albicans Crz1 homolog acting as a downstream target of calcineurin, are required for C. lusitaniae pseudohyphal growth, a process for which the underlying mechanism remains largely unknown in C. lusitaniae but hyphal growth is fundamental to C. albicans virulence. We demonstrate that calcineurin is required for cell wall integrity, ER stress response, optimal growth in serum, virulence in a murine systemic infection model, and antifungal drug tolerance in C. lusitaniae. To further examine the potential of targeting the calcineurin signaling cascade for antifungal drug development, we examined the activity of a calcineurin inhibitor FK506 in combination with caspofungin against echinocandin resistant C. lusitaniae clinical isolates. Broth microdilution and drug disk diffusion assays demonstrate that FK506 has synergistic fungicidal activity with caspofungin against echinocandin resistant isolates. Our findings reveal that pseudohyphal growth is controlled by the calcineurin signaling cascade, and highlight the potential use of calcineurin inhibitors and caspofungin for emerging drug-resistant C. lusitaniae infections.

Indexed as

Drug Resistance, FungalAnimalsAntifungal AgentsCalcineurinCalcineurin InhibitorsCalciumCandidaCandida albicansCandidiasisCaspofunginCell WallColony Count, MicrobialDisease Models, AnimalEchinocandinsEndoplasmic Reticulum StressFungal ProteinsAntifungal AgentsCalcineurinCalcineurin InhibitorsCalciumCaspofunginEchinocandinsFungal ProteinsLipopeptides

Identifiers

PMID22952924
PMCPMC3432075
OpenAlexW1974131997

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.