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Prediction of Potential Drug Targets for Cutaneous Leishmaniasis By Leishmania major and Leishmania tropica: A Quantitative Proteomics and Bioinformatics Approach


Affiliations
1 Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Islamic Republic of
2 Diagnostic Laboratory Sciences and Technology Research Center,Shiraz University of Medical Sciences, Shiraz, Iran, Islamic Republic of
3 Department of Clinical Biochemistry, Zanjan University of Medical Sciences, Zanjan, Iran, Islamic Republic of
 

Leishmania spp. cause life-threatening infectious dis-eases which affect universal health. Novel treatments for leishmaniasis are crucially needed since those available are limited by emerging drug-resistant spe-cies, low efficacy and side effects. In this study, we have employed a quantitative shotgun proteomics and bioinformatics method to identify differentially ex-pressed proteins (DEPs) between Leishmania major and Leishmania tropica and to detect novel potential drug targets for cutaneous leishmaniasis, which may aid in the future drug discovery process. A total of 57 proteins were differentially expressed between the studied species. Based on KEGG pathway analysis, the more upregulated proteins in L. major are clearly re-lated to proteasome and metabolic pathways. In L. tropica, most of the upregulated proteins are related to the metabolic pathway and carbon metabolism. According to gene ontology analysis based on biologi-cal process, the upregulated proteins mainly partici-pated in translation and carbohydrate metabolism in L. tropica and L. major respectively. We have con-structed a protein–protein interaction network that is common for the two species. We detected the top 10 potential targets for drug design by topology analysis of the protein network. Additional in vivo studies are needed to confirm these targets. We have identified several new DEPs between the species which would help in the understanding of pathogenesis mecha-nisms, and offer potential drug targets and vaccine candidates. Analysis of the predicted protein network provides a catalogue of key proteins, which can be considered in future studies to be validated as drug-gable targets against cutaneous leishmaniasis.

Keywords

Cutaneous Leishmaniasis, Leishmania tropica, Leishmania major, Protein Interaction Network, Quantitative Proteomics.
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  • Prediction of Potential Drug Targets for Cutaneous Leishmaniasis By Leishmania major and Leishmania tropica: A Quantitative Proteomics and Bioinformatics Approach

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Authors

Nasrin Amiri-Dashatan
Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Islamic Republic of
Marzieh Ashrafmansouri
Diagnostic Laboratory Sciences and Technology Research Center,Shiraz University of Medical Sciences, Shiraz, Iran, Islamic Republic of
Mostafa Rezaei-Tavirani
Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Islamic Republic of
Mehdi Koushki
Department of Clinical Biochemistry, Zanjan University of Medical Sciences, Zanjan, Iran, Islamic Republic of
Nayebali Ahmadi
Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Islamic Republic of

Abstract


Leishmania spp. cause life-threatening infectious dis-eases which affect universal health. Novel treatments for leishmaniasis are crucially needed since those available are limited by emerging drug-resistant spe-cies, low efficacy and side effects. In this study, we have employed a quantitative shotgun proteomics and bioinformatics method to identify differentially ex-pressed proteins (DEPs) between Leishmania major and Leishmania tropica and to detect novel potential drug targets for cutaneous leishmaniasis, which may aid in the future drug discovery process. A total of 57 proteins were differentially expressed between the studied species. Based on KEGG pathway analysis, the more upregulated proteins in L. major are clearly re-lated to proteasome and metabolic pathways. In L. tropica, most of the upregulated proteins are related to the metabolic pathway and carbon metabolism. According to gene ontology analysis based on biologi-cal process, the upregulated proteins mainly partici-pated in translation and carbohydrate metabolism in L. tropica and L. major respectively. We have con-structed a protein–protein interaction network that is common for the two species. We detected the top 10 potential targets for drug design by topology analysis of the protein network. Additional in vivo studies are needed to confirm these targets. We have identified several new DEPs between the species which would help in the understanding of pathogenesis mecha-nisms, and offer potential drug targets and vaccine candidates. Analysis of the predicted protein network provides a catalogue of key proteins, which can be considered in future studies to be validated as drug-gable targets against cutaneous leishmaniasis.

Keywords


Cutaneous Leishmaniasis, Leishmania tropica, Leishmania major, Protein Interaction Network, Quantitative Proteomics.

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DOI: https://doi.org/10.18520/cs%2Fv120%2Fi6%2F1040-1049