ArticleInternational journal for parasitology. Drugs and drug resistance2013
Molecular characterization of the MRPA transporter and antimony uptake in four New World Leishmania spp. susceptible and resistant to antimony.
Article in International journal for parasitology. Drugs and drug resistance, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Leishmania spp. genetic factors associated with cutaneous leishmaniasis antimony pentavalent drug resistance: a systematic review.Memorias do Instituto Oswaldo Cruz · 2024Pooled it
- Antimony resistance and gene expression inParasitology · 2024Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Transcriptome Analysis of Intracellular Amastigotes of ClinicalMicroorganisms · 2022Article
- Impact of Genetic Diversity and Genome Plasticity ofFrontiers in cellular and infection microbiology · 2022Review
- Antioxidant defence system as a rational target for Chagas disease and Leishmaniasis chemotherapy.Memorias do Instituto Oswaldo Cruz · 2022Review
- Identification of Resistance Determinants for a Promising Antileishmanial Oxaborole Series.Microorganisms · 2021Article
- Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines.Parasites & vectors · 2020Article
- Antileishmanial Aminopyrazoles: Studies into Mechanisms and Stability of Experimental Drug Resistance.Antimicrobial agents and chemotherapy · 2020Article
- The heterologous expression of Escherichia coli MutT enzyme is involved in the protection against oxidative stress in Leishmania braziliensis.Memorias do Instituto Oswaldo Cruz · 2020Article
- Mannosyltransferase (GPI-14) overexpression protects promastigote and amastigote forms of Leishmania braziliensis against trivalent antimony.Parasites & vectors · 2019Article
- RNA-Seq Revealed Expression of Many Novel Genes Associated WithFrontiers in cellular and infection microbiology · 2019Article
- Biophysical and Pharmacological Characterization of Energy-Dependent Efflux of Sb in Laboratory-Selected Resistant Strains ofFrontiers in cell and developmental biology · 2017Article
- A Telomeric Cluster of Antimony Resistance Genes on Chromosome 34 of Leishmania infantum.Antimicrobial agents and chemotherapy · 2016Article
- Intracellular accumulation of Praziquantel in T lymphoblastoid cell lines, CEM (parental) and CEMVBL(P-gp-overexpressing).BMC pharmacology & toxicology · 2016Article
- Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species.Antimicrobial agents and chemotherapy · 2016Article
- The LABCG2 Transporter from the Protozoan Parasite Leishmania Is Involved in Antimony Resistance.Antimicrobial agents and chemotherapy · 2016Article
- Synthesis and characterization of bismuth(III) and antimony(V) porphyrins: high antileishmanial activity against antimony-resistant parasite.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015Article
- Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis.PLoS neglected tropical diseases · 2015Article
- A Multiplatform Metabolomic Approach to the Basis of Antimonial Action and Resistance in Leishmania infantum.PloS one · 2015Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATP-binding cassette (ABC) transporters have been associated with drug resistance in various diseases. The MRPA gene, a transporter of ABCC subfamily, is involved in the resistance by sequestering metal-thiol conjugates in intracellular vesicles of Leishmania parasite. In this study, we performed the molecular characterization of the MRPA transporter, analysis of P-glycoprotein (Pgp) and aquaglyceroporin-1 (AQP1) expression, and determination of antimony level in antimony-susceptible and -resistant lines of L. (V.) guyanensis, L. (L.) amazonensis, L. (V.) braziliensis and L. (L.) infantum. PFGE analysis revealed an association of chromosomal amplification of MRPA gene with the drug resistance phenotype in all SbIII-resistant Leishmania lines analyzed. Levels of mRNA from MRPA gene determined by real-time quantitative RT-PCR showed an increased expression of two fold in SbIII-resistant lines of Leishmania guyanensis, Leishmania amazonensis and Leishmania braziliensis. Western blot analysis revealed that Pgp is increased in the SbIII-resistant L. guyanensis and L. amazonensis lines. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed a reduction in the accumulation of this element in SbIII-resistant L. guyanensis, L. amazonensis and L. braziliensis lines when compared to their susceptible counterparts. Interestingly, a down-regulation of AQP1 protein was observed in the SbIII-resistant L. guyanensis and L. amazonensis lines, contributing for decreasing of SbIII entry in these lines. In addition, efflux experiments revealed that the rates of SbIII efflux are higher in the SbIII-resistant lines of L. guyanensis and L. braziliensis, that may explain also the low SbIII concentration within of these parasites. The BSO, an inhibitor of γ-glutamylcysteine synthetase enzyme, reversed the SbIII-resistance phenotype of L. braziliensis and caused an increasing in the Sb intracellular level in the LbSbR line. Our data indicate that the mechanisms of antimony-resistance are different among species of Leishmania analyzed in this study.
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