ArticleMolecular biology reports2019
Identifying miltefosine-resistant key genes in protein-protein interactions network and experimental verification in Iranian Leishmania major.
Article in Molecular biology reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Omics Approaches in Drug Development against Leishmaniasis: Current Scenario and Future Prospects.Pathogens (Basel, Switzerland) · 2022Review
- Parasite protein phosphatases: biological function, virulence, and host immune evasion.Parasitology research · 2021Review
- An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes.Parasites & vectors · 2020Article
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4 authors.
Funding
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Abstract
Drug resistance is a complex phenomenon during leishmaniasis chemotherapy. In this study, the genes and pathways involved in miltefosine (MIL)-resistant Leishmania were identified using microarray data and in silico approaches. GSE30685 and GSE45496 were obtained from GEO database and analyzed with GEO2R tool to identify genes involved in MIL-resistant Leishmania. 177 differentially expressed genes (DEGs) were selected from these GSEs, which about half of them were uncharacterized/hypothetical proteins. The interactions between DEGs were investigated using STRING database and protein-protein interaction (PPI) networks. Five hub nodes were found in the PPI network. The gene ontology (GO) analysis of the resulting network revealed that DNA replication (GO:0006260) and ATP hydrolysis coupled proton transport (GO:0015991) were the most enriched GO term. Iranian MIL-resistant Leishmania major (L. major) parasites were generated by exposure of wild-type isolates to the increasing concentrations of MIL over a period of 5 months. Proof of mRNA expression levels of the obtained hub genes was assessed in Iranian wild-type and acquired resistant L. major parasites by real-time PCR. A significant higher expression level of LDBPK_150170 (encoding protein phosphatase 2C, PP2C), was only observed in Iranian L. major parasites resistance to MIL. Moreover, the RT-PCR results showed that the expression of metacyclic marker (small hydrophilic endoplasmic reticulum-associated protein, SHERP) and MIL-resistant marker (Leishmania MIL-transporter, LMT) was significantly increased and decreased, respectively, in Iranian MIL-resistant L. major parasites. Taken together, these data suggested that PP2C as well as SHERP and LMT genes may be prospective targets for the treatment of MIL-resistant Leishmania.
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