<scp>MRP</scp>1 mediates folate transport and antifolate sensitivity in <i>Plasmodium falciparum</i>

Rijpma, Sanna R.; Velden, Maarten van der; Bilos, Albert; Jansen, Robert S.; Mahakena, Sunny; Rüssel, Frans G. M.; Sauerwein, Robert W.; Wetering, Koen van de; Koenderink, Jan B.

doi:10.1002/1873-3468.12079

Cited by 15 publications

(28 citation statements)

References 52 publications

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“…None of the Peruvian samples presented mutations on pfk13, pfatg18, pfarps10 and ferredoxin that have been associated with artemisinin resistance 45 , 46 nor pfexo which is associated with piperaquine 47 nor pfmrp1 which is associated with sulfadoxine/pyrimethamine and artemether/lumefantrine resistance 48 .…”

Section: Resultsmentioning

confidence: 91%

Population genomics and evidence of clonal replacement of Plasmodium falciparum in the Peruvian Amazon

Villena

Lizewski

Joya

et al. 2021

Sci Rep

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Previous studies have shown that P. falciparum parasites in South America have undergone population bottlenecks resulting in clonal lineages that are differentially distributed and that have been responsible for several outbreaks different endemic regions. In this study, we explored the genomic profile of 18 P. falciparum samples collected in the Peruvian Amazon Basin (Loreto) and 6 from the Peruvian North Coast (Tumbes). Our results showed the presence of three subpopulations that matched previously typed lineages in Peru: Bv1 (n = 17), Clonet D (n = 4) and Acre-Loreto type (n = 3). Gene coverage analysis showed that none of the Bv1 samples presented coverage for pfhrp2 and pfhrp3. Genotyping of drug resistance markers showed a high prevalence of Chloroquine resistance mutations S1034C/N1042D/D1246Y in pfmdr1 (62.5%) and K45T in pfcrt (87.5%). Mutations associated with sulfadoxine and pyrimethamine treatment failure were found on 88.8% of the Bv1 samples which were triple mutants for pfdhfr (50R/51I/108N) and pfdhps (437G/540E/581G). Analysis of the pfS47 gene that allows P. falciparum to evade mosquito immune responses showed that the Bv1 lineage presented one pfS47 haplotype exclusive to Loreto and another haplotype that was present in both Loreto and Tumbes. Furthermore, a possible expansion of Bv1 was detected since 2011 in Loreto. This replacement could be a result of the high prevalence of CQ resistance polymorphisms in Bv1, which could have provided a selective advantage to the indirect selection pressures driven by the use of CQ for P. vivax treatment.

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Section: Resultsmentioning

confidence: 91%

Population genomics and evidence of clonal replacement of Plasmodium falciparum in the Peruvian Amazon

Villena

Lizewski

Joya

et al. 2021

Sci Rep

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“…Increased expression of pfmrp1 gene has been associated with mefloquine, quinine, and chloroquine resistance. Moreover, this protein has been reported to be involved in the export of folate from malaria parasites into red blood cells [20]. The P. falciparum multidrug resistance gene 1 ( pfmdr1 ) that encodes a P-glycoprotein homologue is also located on the membrane of parasite digestive vacuole, the main target of action of most antimalarial drugs.…”

Section: Discussionmentioning

confidence: 99%

Antimalarial Activity of Piperine

Thiengsusuk

Muhamad

Chai่jaroenkul

et al. 2018

Journal of Tropical Medicine

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Malaria remains a public health problem in tropical and subtropical regions. Resistance of Plasmodium falciparum to artemisinins in Southeast Asia is a great concern for disease control and research on discovery and development of new alternative antimalarial drugs is urgently required. In a previous study, the fruit of Piper chaba Hunt. was demonstrated to exhibit promising antimalarial activity against the asexual stage of 3D7 (chloroquine-sensitive) and K1 (chloroquine-resistant) P. falciparum clones. The aim of the present study was to further investigate the antimalarial activity of piperine, the major isolated constituent of Piper chaba Hunt. fruits against both P. falciparum clones. The antimalarial activity was determined using SYBR green-I-based assay and morphological change was observed under the light microscope with Giemsa staining. The median IC50 (concentration that inhibits parasite growth by 50%) values of piperine against 3D7 and K1 P. falciparum were 111.5 and 59 μM, respectively. A marked change in parasite morphology was observed within 48 hours of piperine exposure. Results of real-time PCR showed no effect of piperine on modulating the expression of the three genes associated with antimalarial drug resistance in P. falciparum, i.e., pfcrt, pfmdr1, and pfmrp1. Piperine could be a promising candidate for further development as an antimalarial drug based on its antimalarial potency and low risk of resistance development.

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“…Surprisingly, a 10 fold increase in methotrexate (MTX) IC 50 response was documented in parallel (190-1800 nM). In a subsequent experiment, adding folate to the medium (10 fold, towards 23 nM) further increased the parasite resistance to MTX (less then 2 fold, IC 50 2700 nM), attesting for the influence of the intracellular pool status (Rijpma et al, 2016a). Data concerning the other antifolate drugs were unfortunately not reported, albeit a similar de-sensitization outcome is expectable.…”

Section: The Folate Pool Factormentioning

confidence: 91%

“…Whatever pf MRP1 and pf MRP2 roles are in P. falciparum physiology, they can be dispensable for the intra-erythocytic cycle. Gene editing experiments have shown that the full deletion of pfmrp1 in W2 ( Raj et al, 2009 ) and NF-54 (the strain from which 3D7 clone was obtained) ( Rijpma et al, 2016 ; Rijpma et al, 2016 ), as well as the pfmrp2 ablation in the latter, renders viable parasites—at least at in vitro conditions, and with these particular clones.…”

Section: Pf Mrp S —Potential Natural Roles In the Parasite Physiologymentioning

confidence: 99%

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Plasmodium falciparum Multidrug Resistance Proteins (pfMRPs)

Gil

Fançony²

2021

Front. Pharmacol.

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The capacity of the lethal Plasmodium falciparum parasite to develop resistance against anti-malarial drugs represents a central challenge in the global control and elimination of malaria. Historically, the action of drug transporters is known to play a pivotal role in the capacity of the parasite to evade drug action. MRPs (Multidrug Resistance Protein) are known in many phylogenetically diverse groups to be related to drug resistance by being able to handle a large range of substrates, including important endogenous substances as glutathione and its conjugates. P. falciparum MRPs are associated with in vivo and in vitro altered drug response, and might be important factors for the development of multi-drug resistance phenotypes, a latent possibility in the present, and future, combination therapy environment. Information on P. falciparum MRPs is scattered in the literature, with no specialized review available. We herein address this issue by reviewing the present state of knowledge.

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MRP1 mediates folate transport and antifolate sensitivity in Plasmodium falciparum

Cited by 15 publications

References 52 publications

Population genomics and evidence of clonal replacement of Plasmodium falciparum in the Peruvian Amazon

Population genomics and evidence of clonal replacement of Plasmodium falciparum in the Peruvian Amazon

Antimalarial Activity of Piperine

Plasmodium falciparum Multidrug Resistance Proteins (pfMRPs)

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