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Biophysical and Pharmacological Characterization of Energy-Dependent Efflux of Sb in Laboratory-Selected Resistant Strains of Leishmania (Viannia) Subgenus

Overview of attention for article published in Frontiers in Cell and Developmental Biology, March 2017
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Title
Biophysical and Pharmacological Characterization of Energy-Dependent Efflux of Sb in Laboratory-Selected Resistant Strains of Leishmania (Viannia) Subgenus
Published in
Frontiers in Cell and Developmental Biology, March 2017
DOI 10.3389/fcell.2017.00024
Pubmed ID
Authors

Priscila G. dos Reis, Rubens L. do Monte-Neto, Maria N. Melo, Frédéric Frézard

Abstract

The growing resistance of leishmaniasis to first-line drugs like antimonials in some regions limits the control of this parasitic disease. The precise mechanisms involved in Leishmania antimony resistance are still subject to debate. The reduction of intracellular Sb(III) accumulation is a common change observed in both laboratory-selected and field isolated resistant Leishmania strains, but the exact transport pathways involved in antimony resistance have not yet been elucidated. In order to functionally characterize the antimony transport routes responsible for resistance, we performed systematic transport studies of Sb(III) in wild-type and resistant strains of L. (Viannia) guyanensis and L. (V.) braziliensis. Those include influx and efflux assays and the influence of ABC transporters and metabolism inhibitors: prochlorperazine, probenecid, verapamil, BSO, and sodium azide. The mRNA levels of genes associated with antimony resistance (MRPA, GSH1, ODC, AQP1, ABCI4, and ARM58) were also investigated in addition to intracellular thiol levels. A strong reduction of Sb influx was observed in L. guyanensis resistant mutant (LgSbR), but not in L. braziliensis (LbSbR). Both mutants showed increased energy-dependent efflux of Sb(III), when compared to their respective parental strains. In LgSbR, BSO and prochlorperazine inhibited antimony efflux and resistance was associated with increased MRPA and GSH1 mRNA levels, while in LbSbR antimony efflux was inhibited by probenicid and prochlorperazine in absence of resistance-associated gene modulation. Intracellular thiol levels were increased in both Sb-resistant mutants. An energy-dependent Sb(III) efflux pathway sensitive to prochlorperazine was clearly evidenced in both Sb-resistant mutants. In conclusion, the present study allowed the biophysical and pharmacological characterization of energy-dependent Sb efflux pathway apparently independent of MRPA, ABCI4, and ARM58 upregulation, in Leishmania (Vianna) mutant selected in vitro for resistance to Sb(III). Prochlorperazine has also been identified as an effective chemosensitizer in both Sb resistant mutants, which acts through inhibition of the active efflux of Sb.

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The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 1 7%
Unknown 14 93%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 20%
Student > Bachelor 3 20%
Student > Master 2 13%
Lecturer 1 7%
Student > Doctoral Student 1 7%
Other 1 7%
Unknown 4 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 20%
Agricultural and Biological Sciences 2 13%
Medicine and Dentistry 2 13%
Business, Management and Accounting 1 7%
Veterinary Science and Veterinary Medicine 1 7%
Other 2 13%
Unknown 4 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 April 2017.
All research outputs
#17,884,576
of 22,961,203 outputs
Outputs from Frontiers in Cell and Developmental Biology
#4,316
of 9,091 outputs
Outputs of similar age
#221,138
of 309,211 outputs
Outputs of similar age from Frontiers in Cell and Developmental Biology
#35
of 45 outputs
Altmetric has tracked 22,961,203 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,091 research outputs from this source. They receive a mean Attention Score of 3.4. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 309,211 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 45 others from the same source and published within six weeks on either side of this one. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.