Evidence map›Paper›PMID 18854164›Full record

ArticleCell2008

Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans.

Oliver W Liu, Cheryl D Chun, Eric D Chow, Changbin Chen, Hiten D Madhani, Suzanne M Noble

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03112031 (A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis), which is not on this map. Cited by 297 papers.

0numbers the graph read from it
0cells of the map it votes in
297citing papers in PubMed
13.4field-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.

NCT03112031 phase2completednot on this mapstarted 2017, after this paper: background citation

A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis

TypeinterventionalSponsorOxford University Clinical Research Unit, VietnamRan2017 to 2018Enrolled50ConditionsMeningitis Streptococcal, Hiv, Meningitis, MeningoencephalitisArmsTamoxifen, Amphotericin B, Fluconazole
3 · Its place in the literature

Who cites it

297 citing papers in PubMed, 449 citations in OpenAlex.

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237 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

6 authors at 1 institution in 1 country.

Oliver W LiuDepartment of Biochemistry and Biophysics, University of California, San Francisco, 600 16th St., GH-N372C, San Francisco, CA 94158, USA.
Cheryl D Chun
Eric D Chow
Changbin Chen
Hiten D Madhani
Suzanne M Noble
University of California, San Francisco · US

Funding

Microbial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5M
Systematic Genetic Analysis of Fungal VirulenceR01AI065519 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MADHANI, HITEN D · 2005 to 2009
$1.7M
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI065519NIAID NIH HHS R01AI065519NIAID NIH HHS T32 AI060537NIAID NIH HHS T32AI060537Wellcome Trust
6 · The paper itself

Abstract

The fungus Cryptococcus neoformans is a leading cause of mortality and morbidity among HIV-infected individuals. We utilized the completed genome sequence and optimized methods for homologous DNA replacement using high-velocity particle bombardment to engineer 1201 gene knockout mutants. We screened this resource in vivo for proliferation in murine lung tissue and in vitro for three well-recognized virulence attributes-polysaccharide capsule formation, melanization, and growth at body temperature. We identified dozens of previously uncharacterized genes that affect these known attributes as well as 40 infectivity mutants without obvious defects in these traits. The latter mutants affect predicted regulatory factors, secreted proteins, and immune-related factors, and represent powerful tools for elucidating novel virulence mechanisms. In particular, we describe a GATA family transcription factor that inhibits phagocytosis by murine macrophages independently of the capsule, indicating a previously unknown mechanism of innate immune modulation.

Indexed as

AnimalsBacterial CapsulesCryptococcosisCryptococcus neoformansGene DeletionHumansLungMelaninsMiceMutagenesis, InsertionalVirulenceMelanins

Identifiers

PMID18854164
PMCPMC2628477
OpenAlexW2001430852

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.