Absence of Association between Methylene Blue Reduced Susceptibility and Polymorphisms in 12 Genes Involved in Antimalarial Drug Resistance in African Plasmodium falciparum

Autor: Mathieu Gendrot, Océane Delandre, Marie Robert, Francis Foguim, Nicolas Benoit, Rémy Amalvict, Isabelle Fonta, Joel Mosnier, Marylin Madamet, Bruno Pradines, on Group
Přispěvatelé: Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA)
Rok vydání: 2021
Předmět:
0301 basic medicine
Drug
media_common.quotation_subject
Plasmodium falciparum
030231 tropical medicine
030106 microbiology
Population
malaria
lcsh:Medicine
lcsh:RS1-441
Pharmaceutical Science
Context (language use)
Drug resistance
Article
lcsh:Pharmacy and materia medica
resistance
03 medical and health sciences
symbols.namesake
0302 clinical medicine
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
parasitic diseases
Drug Discovery
medicine
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Genetic variability
education
media_common
molecular marker
Sanger sequencing
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases
education.field_of_study
biology
lcsh:R
in vitro
biology.organism_classification
medicine.disease
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Virology
3. Good health
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
symbols
methylene blue
Molecular Medicine
Malaria
antimalarial drug
Zdroj: Pharmaceuticals
Pharmaceuticals, 2021, 14 (4), pp.351. ⟨10.3390/ph14040351⟩
Volume 14
Issue 4
Pharmaceuticals, MDPI, 2021, 14 (4), pp.351. ⟨10.3390/ph14040351⟩
Pharmaceuticals, Vol 14, Iss 351, p 351 (2021)
ISSN: 1424-8247
Popis: Half the human population is exposed to malaria. Plasmodium falciparum antimalarial drug resistance monitoring and development of new drugs are major issues related to the control of malaria. Methylene blue (MB), the oldest synthetic antimalarial, is again a promising drug after the break of its use as an antimalarial drug for more than 80 years and a potential partner for triple combination. Very few data are available on the involvement of polymorphisms on genes known to be associated with standard antimalarial drugs and parasite in vitro susceptibility to MB (cross-resistance). In this context, MB susceptibility was evaluated against 482 isolates of imported malaria from Africa by HRP2-based ELISA chemosusceptibility assay. A total of 12 genes involved in antimalarial drug resistance (Pfcrt, Pfdhfr, Pfmdr1, Pfmdr5, Pfmdr6, PfK13, Pfubq, Pfcarl, Pfugt, Pfact, Pfcoronin, and copy number of Pfpm2) were sequenced by Sanger method and quantitative PCR. On the Pfmdr1 gene, the mutation 86Y combined with 184F led to more susceptible isolates to MB (8.0 nM vs. 11.6 nM, p = 0.03). Concerning Pfmdr6, the isolates bearing 12 Asn repetitions were more susceptible to MB (4.6 nM vs. 11.6 nM, p = 0.005). None of the polymorphisms previously described as involved in antimalarial drug resistance was shown to be associated with reduced susceptibility to MB. Some genes (particularly PfK13, Pfugt, Pfact, Pfpm2) did not present enough genetic variability to draw conclusions about their involvement in reduced susceptibility to MB. None of the polymorphisms analyzed by multiple correspondence analysis (MCA) had an impact on the MB susceptibility of the samples successfully included in the analysis. It seems that there is no in vitro cross-resistance between MB and commonly used antimalarial drugs.
Databáze: OpenAIRE
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