Evidence map›Paper›PMID 7991574›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1994

Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans.

J K Lodge, E Jackson-Machelski, D L Toffaletti, J R Perfect, J I Gordon

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
4.9field-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

58 citing papers in PubMed, 170 citations in OpenAlex.

  1. Article
  2. Biolistic Transformation of Cryptococcus neoformans.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  3. Microbiology spectrum · 2023
    Article
  4. Review
  5. Review
  6. Genetic Transformation inJournal of fungi (Basel, Switzerland) · 2021
    Review
  7. Myristate can be used as a carbon and energy source for the asymbiotic growth of arbuscular mycorrhizal fungi.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  8. Review
  9. Article
  10. Review
  11. Virulence Factors as Targets for Anticryptococcal Therapy.Journal of fungi (Basel, Switzerland) · 2016
    Review
  12. Article
  13. Review
  14. The Mechanistic Targets of Antifungal Agents: An Overview.Mini reviews in medicinal chemistry · 2016
    Review
  15. Review
  16. Article
  17. New technology and resources for cryptococcal research.Fungal genetics and biology : FG & B · 2015
    Review
  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 3 institutions in 1 country.

J K LodgeDepartment of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
E Jackson-Machelski
D L Toffaletti
J R Perfect
J I Gordon
Washington University in St. Louis · USDuke Medical Center · USDuke University Hospital · US

Funding

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
ANALOGS OF MYRISTIC ACID TO MODULATE HIV-I ASSEMBLYU01AI027179 · NIAID · WASHINGTON UNIVERSITY · PI GORDON, JEFFREY IVAN · 1988 to 1994
–
MODULATION OF PROTEIN N-MYRISTOYLATION IN MYCO PATHOGENSU01AI030188 · NIAID · WASHINGTON UNIVERSITY · PI GORDON, JEFFREY IVAN · 1990 to 1993
–
NIAID NIH HHS AI27179NIAID NIH HHS AI28388NIAID NIH HHS AI30188
6 · The paper itself

Abstract

Cryptococcus neoformans is a major cause of systemic fungal infection in immunocompromised patients. Myristoyl-CoA:protein N-myristoyltransferase (Nmt) catalyzes the transfer of myristate (C14:0) from myristoyl-CoA to the N-terminal glycine of a subset of cellular proteins produced during vegetative growth of C. neoformans. A Gly487-->Asp mutation was introduced into C. neoformans NMT by targeted gene replacement. The resulting strains are temperature-sensitive myristic acid auxotrophs. They are killed at 37 degrees C when placed in medium lacking myristate and, in an immunosuppressed animal model of cryptococcal meningitis, are completely eliminated from the subarachnoid space within 12 days of initial infection. C. neoformans and human Nmts exhibit differences in their peptide substrate specificities. These differences can be exploited to develop a new class of fungicidal drugs.

Indexed as

Point MutationAcyltransferasesAmino Acid SequenceAnimalsAspartic AcidBase SequenceCryptococcus neoformansDNA PrimersGenetic TechniquesGlycineHumansKineticsMeningitis, CryptococcalMolecular Sequence DataMutagenesis, Site-DirectedPolymerase Chain ReactionAcyltransferasesAspartic AcidDNA PrimersGlycineglycylpeptide N-tetradecanoyltransferaseRecombinant Proteins

Identifiers

PMID7991574
PMCPMC45365
OpenAlexW1985052951

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.