Identification of differential protein expression and putative drug target in metacyclic stage of Leishmania major and Leishmania tropica: A quantitative proteomics and computational view |
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| Affiliation: | 1. Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran;1. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Medical Parasitology and Mycology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran;3. Department of Geography, Ardabil Branch, Islamic Azad University, Ardabil, Iran;4. Genetic Engineering and Biotechnology Research Institute University of Sadat City Sadat, Egypt;5. Department of Parasitology and Mycology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran;6. Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran;7. Department of Medical Microbiology and Parasitology, College of Health Sciences, Bayero University, PMB 3011, Kano, Nigeria;8. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran;9. Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;10. Department of Basic Sciences of Veterinary Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Iran;11. Department of Parasitology, School of Allied Medical Sciences. Ilam University of Medical Sciences, Ilam, Iran;1. Doctorate Student in the Northeast Network in Biotechnology, State University of Ceará, Fortaleza, Ceará, Brazil;2. Embrapa Goats and Sheep, Sobral, Ceará, Brazil;3. Scholarship for Regional Scientific Development of the National Council for Scientific and Technological Development (DCR-CNPq/FUNCAP), Level C, Brasilia, Distrito Federal, Brazil;4. Embrapa Pigs and Poultry, Concórdia, Santa Catarina, Brazil;5. Doctor in Veterinary Sciences, State University of Ceará, Fortaleza, Ceará, Brazil;6. Doctorate Student in Animal Science, Federal University of Piauí, Teresina, Piauí, Brazil;7. Master Degree Student Medical Microbiology, Federal University of Ceará, Fortaleza, Brazil;8. Undergraduate Student in Zootechnics, State University of Acaraú Valley, Sobral, Ceará, Brazil;9. Undergraduate Student in Biological Sciences, State University of Acaraú Valley, Sobral, Ceará, Brazil;10. State University of Ceará, Fortaleza, Ceará, Brazil;1. Department of Clinical Sciences, Faculty of Veterinary Medicine, Sanandaj Branch Islamic Azad University, Sanandaj, Iran;2. Department of Microbiology, Faculty of Veterinary Medicine, Sanandaj Branch Islamic Azad University, Sanandaj, Iran;1. Razi Vaccine and Serum Research Institute (RVSRI), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran;2. Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran;3. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;1. Laboratório de Zoonoses Bacterianas, Departamento de Medicina Veterinária Preventiva e Saúde Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brazil;2. Médico Veterinário, Auditor Fiscal Agropecuário, Agência de Defesa e Inspeção Agropecuária do Estado do Amapá, AP, Brazil;3. Laboratório de Biotecnologia Medicinal, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapá, AP, Brazil;4. Curso de Medicina Veterinária, Universidade Santo Amaro, São Paulo, Brazil |
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| Abstract: | Cutaneous leishmaniasis (CL) is an infectious disease that commonly caused by Leishmania (L.) major and L.tropica. Recently there has been a growing interest in proteomics analysis on Leishmania for drug target discovery. Therefore, we aimed to distinguish proteins which might be characteristic for each of the species from those shared by both to the detection of drug targets, which may become helpful for designing new drugs for CL. To identify differences in protein profiles of L. major and L. tropica, we conducted a Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) analysis. Totally 67 differentially expressed proteins (DEPs) (fold change> 2 and p < 0.05) were identified between species. Of these, 42 and 25 proteins were up-regulated in L. major and L. tropica, respectively. Several enriched GO terms were identified via biological process of up-regulated proteins. Furthermore, the small molecule metabolic process and translation were detected as significant biological processes for up-regulated proteins in L. major, while translation was identified for L. tropica. Also, KEGG analysis has revealed glycolysis/gluconeogenesis and translation as the top pathways in the proteins up-regulated in L. major and L. tropica, respectively. Finally glycosomal malate dehydrogenase was identified as putative drug target using network and homology analyses. The DEPs between the species are essential in host-pathogen interactions and parasite survival in the macrophage. Furthermore, L. major and L. tropica possibly uses different pathogenicity mechanisms that leads to anthroponotic or zoonotic CL. Our results may help in the drug discovery and chemotherapeutic interventions. |
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| Keywords: | Cutaneous leishmaniasis Shotgun proteomics Protein interaction Drug discovery |
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