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Selection of an Aptamer against the Enzyme 1-deoxy-D-xylulose-5-phosphate Reductoisomerase from Plasmodium falciparum

Authors :
Carlota Roca
Yunuen Avalos-Padilla
Beatriz Prieto-Simón
Valentín Iglesias
Miriam Ramírez
Santiago Imperial
Xavier Fernàndez-Busquets
Source :
Pharmaceutics, Vol 14, Iss 11, p 2515 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

The methyl erythritol phosphate (MEP) pathway of isoprenoid biosynthesis is essential for malaria parasites and also for several human pathogenic bacteria, thus representing an interesting target for future antimalarials and antibiotics and for diagnostic strategies. We have developed a DNA aptamer (D10) against Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), the second enzyme of this metabolic route. D10 binds in vitro to recombinant DXR from P. falciparum and Escherichia coli, showing at 10 µM a ca. 50% inhibition of the bacterial enzyme. In silico docking analysis indicates that D10 associates with DXR in solvent-exposed regions outside the active center pocket. According to fluorescence confocal microscopy data, this aptamer specifically targets in P. falciparum in vitro cultures the apicoplast organelle where the MEP pathway is localized and is, therefore, a highly specific marker of red blood cells parasitized by Plasmodium vs. naïve erythrocytes. D10 is also selective for the detection of MEP+ bacteria (e.g., E. coli and Pseudomonas aeruginosa) vs. those lacking DXR (e.g., Enterococcus faecalis). Based on these results, we discuss the potential of DNA aptamers in the development of ligands that can outcompete the performance of the well-established antibody technology for future therapeutic and diagnostic approaches.

Details

Language :
English
ISSN :
14112515 and 19994923
Volume :
14
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.5df771176394415fbdf913a9d7b24752
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics14112515