Evidence map›Paper›PMID 18259613›Full record

ArticleThe Journal of clinical investigation2008

PI3K signaling of autophagy is required for starvation tolerance and virulenceof Cryptococcus neoformans.

Guowu Hu, Moshe Hacham, Scott R Waterman, John Panepinto, Soowan Shin, Xiaoguang Liu, Jack Gibbons, Tibor Valyi-Nagy, Keisuke Obara, H Ari Jaffe and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
15.8field-weighted citation impact, top 1% 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

70 citing papers in PubMed, 214 citations in OpenAlex.

  1. Multifunctional Roles of Autophagy in Fungi.Journal of fungi (Basel, Switzerland) · 2026
    Review
  2. Article
  3. Article
  4. Roles of theJournal of fungi (Basel, Switzerland) · 2025
    Article
  5. United toward a common goal: Coordination of microbial virulence phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Arg1 frommBio · 2024
    Article
  7. Article
  8. Article
  9. Article
  10. Class III PI3K Biology.Current topics in microbiology and immunology · 2022
    Article
  11. Article
  12. Article
  13. Autophagy Regulates Fungal Virulence and Sexual Reproduction inFrontiers in cell and developmental biology · 2020
    Article
  14. Article
  15. Article
  16. Pathogenic Fungal Infection in the Lung.Frontiers in immunology · 2019
    Review
  17. Article
  18. Protein Kinases at the Intersection of Translation and Virulence.Frontiers in cellular and infection microbiology · 2019
    Review
  19. Infection and immunity · 2018
    Article
  20. Review

10 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 2 countries.

Guowu HuSection of Infectious Diseases, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Moshe Hacham
Scott R Waterman
John Panepinto
Soowan Shin
Xiaoguang Liu
Jack Gibbons
Tibor Valyi-Nagy
Keisuke Obara
H Ari Jaffe
Yoshinori Ohsumi
Peter R Williamson
University of Illinois Chicago · USNational Institute for Basic Biology · JP

Funding

The Role of Unc119 in T Cell Antigen Receptor Signaling1R01AI045995 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI COOK, JAMES LOWELL · 1999 to 2009
$2.6M
AN AIDS-RELATED CRYPTOCOCCUS NEOFORMANS GENOME CENTERU01AI047087 · NIAID · STANFORD UNIVERSITY · PI DAVIS, RONALD WAYNE · 2000 to 2002
$2.6M
Virulence Factor Trafficking in CryptococcusR01AI049371 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI WILLIAMSON, PETER RICHARD · 2002 to 2005
$1.2M
NIAID NIH HHS AI45995NIAID NIH HHS AI47087NIAID NIH HHS AI49371NIAID NIH HHS R01 AI045995NIAID NIH HHS R01 AI049371
6 · The paper itself

Abstract

Autophagy is a process by which cells recycle cytoplasm and defective organelles during stress situations such as nutrient starvation. It can also be used by host cells as an immune defense mechanism to eliminate infectious pathogens. Here we describe the use of autophagy as a survival mechanism and virulence-associated trait by the human fungal pathogen Cryptococcus neoformans. We report that a mutant form of C. neoformans lacking the Vps34 PI3K (vps34Delta), which is known to be involved in autophagy in ascomycete yeast, was defective in the formation of autophagy-related 8-labeled (Atg8-labeled) vesicles and showed a dramatic attenuation in virulence in mouse models of infection. In addition, autophagic vesicles were observed in WT but not vps34Delta cells after phagocytosis by a murine macrophage cell line, and Atg8 expression was exhibited in WT C. neoformans during human infection of brain. To dissect the contribution of defective autophagy in vps34Delta C. neoformans during pathogenesis, a strain of C. neoformans in which Atg8 expression was knocked down by RNA interference was constructed and these fungi also demonstrated markedly attenuated virulence in a mouse model of infection. These results demonstrated PI3K signaling and autophagy as a virulence-associated trait and survival mechanism during infection with a fungal pathogen. Moreover, the data show that molecular dissection of such pathogen stress-response pathways may identify new approaches for chemotherapeutic interventions.

Indexed as

AutophagyAnimalsCell LineCryptococcus neoformansMacrophagesMicePhosphatidylinositol 3-KinasesSignal TransductionVirulencePhosphatidylinositol 3-Kinases

Identifiers

PMID18259613
PMCPMC2230655
OpenAlexW2111715441

What OpenQuestion holds

Textmetadata
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.