Comparative Two-dimensional Gel Electrophoresis Maps for Amastigote-like Proteomes of Iranian Leishmania Tropica and Leishmania major Isolates

Ashrafmansouri, Marzieh; Sadjjadi, Fatemeh Sadat; Seyyedtabaei, Seyyedjavad; Haghighi, Ali; Rezaei‐Tavirani, Mostafa; Ahmadi, Nayeb Ali

doi:10.31661/gmj.v8i0.1520

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…It was concluded that the levels of protein expression in the amastigote form of L. tropica and L. major strains were distinct. It was found that the use of proteomics tools, statistical analysis of Leishmania’s proteome in Iranian isolates, and comparison of their protein expression levels could aid researchers in developing a more accurate diagnosis and treatment for the disease [ 65 ].…”

Section: Proteomic Analysis Of Different Leishmania Speciesmentioning

confidence: 99%

Omics Approaches in Drug Development against Leishmaniasis: Current Scenario and Future Prospects

Rabaan

Bakhrebah

Mohapatra³

et al. 2022

Pathogens

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Leishmaniasis is a zoonotic disease transmitted in humans by the bite of Leishmania-infected phlebotomine sandflies. Each year approximately 58,500 cases of leishmaniasis are diagnosed across the globe, with a mortality rate of nearly seven percent. There are over 20 parasitic strains of Leishmania which are known to cause distinct types of leishmaniasis and pose an endemic threat to humans worldwide. Therefore, it is crucial to develop potential medications and vaccines to combat leishmaniasis. However, the task of developing therapeutic solutions is challenging due to Leishmania's digenetic lifecycle. The challenge is further intensified by cases of resistance against the available drugs. Owing to these challenges, the conventional drug development regimen is further limited by target discovery and ligand suitability for the targets. On the other hand, as an added advantage, the emergence of omics-based tools, such as high-end proteomics, transcriptomics and genomics, has hastened the pace of target discovery and target-based drug development. It is now becoming apparent that multi-omics convergence and an inter-connected systems approach is less time-consuming and more cost-effective for any drug-development process. This comprehensive review is an attempt to summarize the current knowledge on the muti-omics approach in drug development against leishmaniasis. In particular, it elaborates the potential target identification from secreted proteins in various stages of Leishmania infection and also illustrates the convergence of transcriptomic and genomic data towards the collective goal of drug discovery. This review also provides an understanding of the potential parasite’s drug targets and drug resistance characteristics of the parasite, which can be used in designing effective and specific therapeutics.

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Section: Proteomic Analysis Of Different Leishmania Speciesmentioning

confidence: 99%

Omics Approaches in Drug Development against Leishmaniasis: Current Scenario and Future Prospects

Rabaan

Bakhrebah

Mohapatra³

et al. 2022

Pathogens

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“…In the field of the molecular differences between procyclic, metacyclic and amastigote forms, several investigation was reported the proteome of promastigotes and amastigotes forms of L. major , L. infantum , L. donovani and L. Mexicana . Most of these reports have used 2DE map to detect global differences of Leishmania species life stages (Amiri-Dashatan et al 2020b ; Ashrafmansouri et al 2019 ), which may be due to post-translational modifications (PTMs) affect charged amino acids (Rosenzweig et al 2008 ). Therefore, gel free approaches provide a valuable resource to higher proteome coverage and more precise quantitative information.…”

Section: Introductionmentioning

confidence: 99%

Identification of protein profile in metacyclic and amastigote-like stages of Leishmania tropica: a proteomic approach

2022

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Leishmaniasis is a tropical disease that leads to various clinical phenotypes. This study aimed to investigate protein expression changes in metacyclic and amastigote-like stages of L. tropica isolated from Iranian cutaneous leishmaniasis patients. Isolated samples were cultured and species type identified using PCR–RFLP technique. The promastigotes were grown in RPMI1640 media and differentiated to metacyclic and amastigote-like forms, followed by the extracted proteins of both successive stages carried out for proteomics and bioinformatics analysis. Using SWATH-MS quantitative proteomics technique, a total 176 and 155 distinct proteins were identified in metacyclic and axenic amastigote stages, respectively. Of these, 65 proteins were altered significantly (p-value < 0.05 and fold change ≥ 2) between studied stages. Several gene ontology (GO) categories were enriched for biological process during conversion of metacyclic promastigotes into amastigote-like, which “metabolic process” (GO: 0044281, P-Value: 6.52e-5), and “translation” (GO: 0006412, p-value: 5.01e–14) were disclosed as the top category in up and down-regulated proteins, respectively. Also, the KEGG pathway analysis indicated “metabolic pathways” and “ribosome” term as the most important pathways in up and down-regulated proteins, respectively. According to protein interaction network analysis, enolase (ENOL) has been detected as main hub proteins during differentiation, followed by Putative NADH-dependent fumarate reductase (LmjF.35.1180) and 40S ribosomal protein S2 (LmjF.32.0450). Overall, protein changes possibly play important roles in L. tropica biology. Anabolic pathways were down-regulated, whereas catabolic pathways were up-regulated during L. tropica differentiation. These protein expression changes could provide parasite survival in host macrophages, and could use as novel potential drug and vaccine targets for leishmaniasis. Graphical Abstract

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“…infantum, L. donovani and L. Mexicana. Most of these investigations used 2DE map to detect global differences of different life stages of different species [14], which may be due to post-translational modifications (PTMs) affect charged amino acids [15].Therefore, gel free approaches provide a significant resource to higher proteome coverage and more precise quantitative information. SWATH is a recently developed label free quantitative method, in which data independent acquisition is coupled with peptide spectral library match [16,17].…”

Section: Introductionmentioning

confidence: 99%

Identification of proteins in promastigote and amastigote-like stages of Leishmania tropica by a quantitative proteomic approach

Ashrafmansouri¹,

Amiri-Dashatan²,

Ahmadi³

2019

Preprint

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Background Leishmania parasites differentiate into the infective metacyclic form in the sand-fly and following is transformed to the amastigote in the host cells. The aims of this study were to identified differentially regulated proteins in the metacyclic and amastigote-like stages of L. tropica, and investigate their potential role in differentiation and pathogenesis molecular mechanisms.Methods The samples were cultured and identified by using PCR-RFLP technique. We employed We employed Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) to identify differentially regulated proteins between the metacyclic and amastigote-like stages of L. tropica.Results A total 176 and 155 distinct proteins were identified in metacyclic and axenic amastigote, respectively. Of these, 65 proteins were altered at least 2 folds. Proteins that were up- or down-regulated included energy production, lipid and amino acid metabolism, heat shock proteins, mRNA processing proteins, glycolytic and translational activity proteins. Several enriched GO terms were identified via biological process analyses, which “metabolic process” (GO: 0044281, P-Value: 6.52e-5), and “translation” (GO: 0006412, p-value: 5.01e-14) were disclosed as top category in up and down-regulated proteins, respectively. Also, the KEGG analysis indicated “metabolic pathways” and “ribosome” term as the top pathways in up and down-regulated proteins, respectively.Conclusions This study provides the first quantitative analysis of protein expression during differentiation from metacyclic to amastigote-like of L. tropica. In conclusion, anabolic pathways were down-regulated, whereas catabolic pathways were up-regulated during L. tropica differentiation in order to parasite survival in host macrophages, in which these changes can be used as novel potential targets for the infection management.

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Comparative Two-dimensional Gel Electrophoresis Maps for Amastigote-like Proteomes of Iranian Leishmania Tropica and Leishmania major Isolates

Cited by 5 publications

References 19 publications

Omics Approaches in Drug Development against Leishmaniasis: Current Scenario and Future Prospects

Omics Approaches in Drug Development against Leishmaniasis: Current Scenario and Future Prospects

Identification of protein profile in metacyclic and amastigote-like stages of Leishmania tropica: a proteomic approach

Identification of proteins in promastigote and amastigote-like stages of Leishmania tropica by a quantitative proteomic approach

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