Evidence map›Paper›PMID 23114753›Full record

ArticleAntimicrobial agents and chemotherapy2013

Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and application of statins as a novel effective therapeutic approach against Acanthamoeba infections.

Carmen María Martín-Navarro, Jacob Lorenzo-Morales, Rubén P Machin, Atteneri López-Arencibia, José Manuel García-Castellano, Isabel de Fuentes, Brendan Loftus, Sutherland K Maciver, Basilio Valladares, José E Piñero

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

18 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Parasitology · 2020
    Article
  6. Article
  7. Drug Discovery againstPathogens (Basel, Switzerland) · 2020
    Review
  8. Acanthamoeba encephalitis in immunocompetent hosts: A report of two cases.Journal of family medicine and primary care · 2020
    Article
  9. In Vitro Activity of Statins againstPathogens (Basel, Switzerland) · 2019
    Article
  10. Pathogens (Basel, Switzerland) · 2019
    Article
  11. Statins Perturb GMolecular pharmacology · 2019
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. 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

10 authors at 6 institutions in 3 countries.

Carmen María Martín-NavarroUniversity Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain. cmmartin@ull.es
Jacob Lorenzo-Morales
Rubén P Machin
Atteneri López-Arencibia
José Manuel García-Castellano
Isabel de Fuentes
Brendan Loftus
Sutherland K Maciver
Basilio Valladares
José E Piñero
Universidad de La Laguna · ESHospital Universitario de Gran Canaria Doctor Negrín · ESHospital Universitario Insular de Gran Canaria · ESInstituto de Salud Carlos III · ESUniversity College Dublin · IEUniversity of Edinburgh · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acanthamoeba is an opportunistic pathogen in humans, whose infections most commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target in Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluated in vitro against three clinical strains of Acanthamoeba by using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA and Acanthamoeba treatment using statins is a novel powerful treatment option against Acanthamoeba species in human disease.

Indexed as

Acanthamoeba castellaniiAcyl Coenzyme AAmino Acid SequenceCatalytic DomainCell ProliferationCells, CulturedEnzyme AssaysHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl-CoA-Reductases, NADP-dependentInhibitory Concentration 50Mevalonic AcidMolecular Sequence DataProtozoan ProteinsRNA, Small Interfering3-hydroxy-3-methylglutaryl-coenzyme AAcyl Coenzyme AHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl-CoA-Reductases, NADP-dependentMevalonic AcidProtozoan ProteinsRNA, Small Interfering

Identifiers

PMID23114753
PMCPMC3535909
OpenAlexW2141231972

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.