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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Plasmodium falciparum Acetyl-CoA Synthetase Is Essential for Parasite Intraerythrocytic Development and Chromatin Modification

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Author(s):
Prata, Isadora Oliveira [1] ; Galindo Cubillos, Eliana Fernanda [1] ; Kruger, Arne [1] ; Barbosa, Deibs [2] ; Martins, Joaquim [2] ; Setubal, Joao Carlos [2] ; Wunderlich, Gerhard [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508000 Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: ACS INFECTIOUS DISEASES; v. 7, n. 12, p. 3224-3240, DEC 10 2021.
Web of Science Citations: 0
Abstract

The malaria parasite Plasmodium falciparum possesses a unique Acetyl-CoA Synthetase (PfACS), which provides acetyl moieties for different metabolic and regulatory cellular pathways. We characterized PfACS and studied its role focusing on epigenetic modifications using the var gene family as reporter genes. For this, mutant lines to modulate plasmodial ACS expression by degronmediated protein degradation and ribozyme-induced transcript decay were created. Additionally, an inhibitor of the human Acetyl-CoA Synthetase 2 was tested for its effectiveness in interfering with PfACS. The knockdown of PfACS or its inhibition resulted in impaired parasite growth. Decreased levels of PfACS also led to differential histone acetylation patterns, altered variant gene expression, and concomitantly decreased cytoadherence of infected red blood cells containing knocked-down parasites. Further, ChIP analysis revealed the presence of PfACS in many loci in ring stage parasites, underscoring its involvement in the regulation of chromatin. Due to its central function in the plasmodial metabolism and significant differences to human ACS, PfACS is an interesting target for drug development. (AU)

FAPESP's process: 17/24267-7 - Role of chromatin modifiers in the transcription dynamics of virulence factors of the human malaria parasite Plasmodium falciparum
Grantee:Gerhard Wunderlich
Support Opportunities: Regular Research Grants
FAPESP's process: 16/12659-5 - Approaching the role of three ApiAP2 transcription factors in the control of gene transcription in intraerythrocytic and sexual stages of Plasmodium falciparum
Grantee:Eliana Fernanda Galindo Cubillos
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/08820-0 - Nanoparticle-assisted drug delivery of Vitamin B6 pathway inhibitors in malaria
Grantee:Arne Kruger
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
Grantee:Carsten Wrenger
Support Opportunities: Research Projects - Thematic Grants