Evidence map›Paper›PMID 39558417›Full record

ArticleParasites & vectors2024

Ascorbate peroxidase modulation confirms key role in Leishmania infantum oxidative defence.

Isabella Fernandes Martins Santos, Douglas de Souza Moreira, Karla Ferreira Costa, Juliana Martins Ribeiro, Silvane Maria Fonseca Murta, Ana Maria Murta Santi

Abstract read
In one paragraph

Article in Parasites & vectors, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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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.

Isabella Fernandes Martins Santos *Grupo de Genômica funcional de Parasitos (GFP), Instituto René Rachou IRR, Fundação Oswaldo Cruz - FIOCRUZ/Minas, Avenida Augusto de Lima 1715, Belo Horizonte, MG, 30190-002, Brazil.
Douglas de Souza Moreira *Grupo de Genômica funcional de Parasitos (GFP), Instituto René Rachou IRR, Fundação Oswaldo Cruz - FIOCRUZ/Minas, Avenida Augusto de Lima 1715, Belo Horizonte, MG, 30190-002, Brazil.
Karla Ferreira CostaGrupo de Genômica funcional de Parasitos (GFP), Instituto René Rachou IRR, Fundação Oswaldo Cruz - FIOCRUZ/Minas, Avenida Augusto de Lima 1715, Belo Horizonte, MG, 30190-002, Brazil.
Juliana Martins RibeiroGrupo de Genômica funcional de Parasitos (GFP), Instituto René Rachou IRR, Fundação Oswaldo Cruz - FIOCRUZ/Minas, Avenida Augusto de Lima 1715, Belo Horizonte, MG, 30190-002, Brazil.
Silvane Maria Fonseca MurtaGrupo de Genômica funcional de Parasitos (GFP), Instituto René Rachou IRR, Fundação Oswaldo Cruz - FIOCRUZ/Minas, Avenida Augusto de Lima 1715, Belo Horizonte, MG, 30190-002, Brazil. silvane.murta@fiocruz.br.
Ana Maria Murta SantiGrupo de Genômica funcional de Parasitos (GFP), Instituto René Rachou IRR, Fundação Oswaldo Cruz - FIOCRUZ/Minas, Avenida Augusto de Lima 1715, Belo Horizonte, MG, 30190-002, Brazil. anamms552@gmail.com.

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq 309994-2023-3Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Finance Code 001Fundação de Amparo à Pesquisa do Estado de Minas Gerais APQ-02816-21; BDP-00657; RED-00104-22Fundação Oswaldo Cruz Chamada de Redes Colaborativas de Pesquisa do Instituto René Rachou-Fiocruz Minas (Rede FarVac )
6 · The paper itself

Abstract

backgroundAscorbate peroxidase (APX) has emerged as a promising target for chemotherapy because of its absence in humans and crucial role in the antioxidant defence of trypanosomatids. APXs, which are class I haeme-containing enzymes, reduces hydrogen peroxide using ascorbate to produce water and monodehydroascorbate, thereby preventing cell damage caused by H

methodsWe aimed to create an APX-knockout L. infantum line using CRISPR/Cas9. Despite unsuccessful attempts at full knockouts, we achieved deletion of chromosomal copies post-APX episomal insertion, yielding LiΔchrAPX::LbAPX parasites. We performed phenotypic characterization to assess the impact of these genetic modifications, which included the determination of APX transcript expression levels using quantitative PCR, drug sensitivity, infectivity, and parasite survival in macrophages.

resultsQuantitative polymerase chain reaction (PCR) analysis revealed a 10- to 13-fold reduction in APX transcript expression in LiΔchrAPX::LbAPX compared with wild-type (LiWT) and APX-overexpressing (Li::Cas9::LbAPX) parasites, respectively. The episomes in those knockdown parasites remained stable even after 20 drug-free passages in vitro. Li::Cas9::LbAPX parasites showed increased resistance to trivalent antimony (Sb

conclusionsOur findings hint at the indispensability of APX in L. infantum and raise the possibility of its potential as a therapeutic target for leishmaniasis.

Indexed as

Ascorbate PeroxidasesLeishmania infantumMacrophagesOxidative StressAnimalsAntiprotozoal AgentsCRISPR-Cas SystemsDrug ResistanceGene Knockout TechniquesHydrogen PeroxideMiceProtozoan ProteinsAntiprotozoal AgentsAscorbate PeroxidasesHydrogen PeroxideProtozoan ProteinsAntioxidant defenceAscorbate peroxidaseCRISPR/Cas9Drug resistanceLeishmania infantum

Identifiers

PMID39558417
PMCPMC11575162

What Socratic 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 Socratic graph.