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Comparative mitochondrial proteomics of Leishmania tropica clinical isolates resistant and sensitive to meglumine antimoniate

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Abstract

Antimony is an important drug for the treatment of Leishmania parasite infections. In several countries, the emergence of drug-resistant Leishmania species has reduced the effectiveness of this drug. The mechanism of clinical drug resistance is unclear. The aim of this work was to identify mitochondrial proteome alterations associated with resistance against antimonial. A combination of cell fractionation, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and Label-Free Quantification was used to characterize the mitochondrial protein composition of Leishmania tropica field isolates resistant and sensitive to meglumine antimoniate. LC-MS/MS analysis resulted in the identification of about 1200 proteins of the Leishmania tropica mitochondrial proteome. Various criteria were used to allocate about 40% proteins to mitochondrial proteome. Comparative quantitative proteomic analysis of the sensitive and the resistant strains showed proteins with differential abundance in resistance species are involved in TCA and aerobic respiration enzymes, stress proteins, lipid metabolism enzymes, and translation. These results showed that the mechanism of antimony resistance in Leishmania spp. field isolate may be associated with alteration in enzymes involved in mitochondrial pathways.

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Acknowledgments

We express our sincere thanks to Dr. Marc Ouellete for proof-reading and revising the final draft of the manuscript.

Funding

This research is a part of Ph.D thesis of first author and was supported by Grant No.28625 from Iran University of Medical Sciences (IUMS), Tehran, Iran.

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Authors and Affiliations

  1. Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Minoo Tasbihi & Ramtin Hadighi

  2. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

    Faezeh Shekari

  3. Department of Biology, University of Science and Culture, Tehran, Iran

    Faezeh Shekari

  4. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Homa Hajjaran

  5. Department of Laboratory Science, Marand Branch, Islamic Azad University, Marand, Iran

    Majid Khanmohammadi

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  1. Minoo Tasbihi
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  2. Faezeh Shekari
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  3. Homa Hajjaran
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  4. Majid Khanmohammadi
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  5. Ramtin Hadighi
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Contributions

1. Conceived and designed the experiments: RH FSH MT HH.

2. Performed the experiments: MT FSH.

3. Analyzed the data: MT FSH RH.

4. Wrote and revised the paper: MT FSH RH MKh.

5. All authors read and approved the final manuscript.

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Correspondence to Faezeh Shekari or Ramtin Hadighi.

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Tasbihi, M., Shekari, F., Hajjaran, H. et al. Comparative mitochondrial proteomics of Leishmania tropica clinical isolates resistant and sensitive to meglumine antimoniate. Parasitol Res 119, 1857–1871 (2020). https://doi.org/10.1007/s00436-020-06671-x

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