In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity
Leishmaniasis is a neglected tropical disease caused by <i>Leishmania</i> spp. The improvement of existing treatments and the discovery of new drugs remain ones of the major goals in control and eradication of this disease. From the parasite genome, we have identified the homologue of th...
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/22/12592 |
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| author | Miriam Algarabel Celia Fernández-Rubio Katerina Musilova José Peña-Guerrero Andrés Vacas Esther Larrea Paul A. Nguewa |
| author_facet | Miriam Algarabel Celia Fernández-Rubio Katerina Musilova José Peña-Guerrero Andrés Vacas Esther Larrea Paul A. Nguewa |
| author_sort | Miriam Algarabel |
| collection | DOAJ |
| description | Leishmaniasis is a neglected tropical disease caused by <i>Leishmania</i> spp. The improvement of existing treatments and the discovery of new drugs remain ones of the major goals in control and eradication of this disease. From the parasite genome, we have identified the homologue of the human oncogene <i>PES1</i> in <i>Leishmania major</i> (<i>LmjPES</i>). It has been demonstrated that PES1 is involved in several processes such as ribosome biogenesis, cell proliferation and genetic transcription. Our phylogenetic studies showed that <i>LmjPES</i> encodes a highly conserved protein containing three main domains: PES N-terminus (shared with proteins involved in ribosomal biogenesis), BRCT (found in proteins related to DNA repair processes) and MAEBL-type domain (C-terminus, related to erythrocyte invasion in apicomplexan). This gene showed its highest expression level in metacyclic promastigotes, the infective forms; by fluorescence microscopy assay, we demonstrated the nuclear localization of LmjPES protein. After generating mutant parasites overexpressing <i>LmjPES</i>, we observed that these clones displayed a dramatic increase in the ratio of cell infection within macrophages. Furthermore, BALB/c mice infected with these transgenic parasites exhibited higher footpad inflammation compared to those inoculated with non-overexpressing parasites. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T05:24:49Z |
| publishDate | 2021-11-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-82c3ee98cb5044c4b6784b143f7162442023-11-22T23:44:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221259210.3390/ijms222212592In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite InfectivityMiriam Algarabel0Celia Fernández-Rubio1Katerina Musilova2José Peña-Guerrero3Andrés Vacas4Esther Larrea5Paul A. Nguewa6Department of Microbiology and Parasitology, ISTUN Instituto de Salud Tropical, IdiSNA, Instituto de Investigación Sanitaria de Navarra, Universidad de Navarra, E-31008 Pamplona, SpainDepartment of Microbiology and Parasitology, ISTUN Instituto de Salud Tropical, IdiSNA, Instituto de Investigación Sanitaria de Navarra, Universidad de Navarra, E-31008 Pamplona, SpainDepartment of Microbiology and Parasitology, ISTUN Instituto de Salud Tropical, IdiSNA, Instituto de Investigación Sanitaria de Navarra, Universidad de Navarra, E-31008 Pamplona, SpainDepartment of Microbiology and Parasitology, ISTUN Instituto de Salud Tropical, IdiSNA, Instituto de Investigación Sanitaria de Navarra, Universidad de Navarra, E-31008 Pamplona, SpainDepartment of Microbiology and Parasitology, ISTUN Instituto de Salud Tropical, IdiSNA, Instituto de Investigación Sanitaria de Navarra, Universidad de Navarra, E-31008 Pamplona, SpainISTUN Instituto de Salud Tropical, IdiSNA, Instituto de Investigación Sanitaria de Navarra, Universidad de Navarra, E-31008 Pamplona, SpainDepartment of Microbiology and Parasitology, ISTUN Instituto de Salud Tropical, IdiSNA, Instituto de Investigación Sanitaria de Navarra, Universidad de Navarra, E-31008 Pamplona, SpainLeishmaniasis is a neglected tropical disease caused by <i>Leishmania</i> spp. The improvement of existing treatments and the discovery of new drugs remain ones of the major goals in control and eradication of this disease. From the parasite genome, we have identified the homologue of the human oncogene <i>PES1</i> in <i>Leishmania major</i> (<i>LmjPES</i>). It has been demonstrated that PES1 is involved in several processes such as ribosome biogenesis, cell proliferation and genetic transcription. Our phylogenetic studies showed that <i>LmjPES</i> encodes a highly conserved protein containing three main domains: PES N-terminus (shared with proteins involved in ribosomal biogenesis), BRCT (found in proteins related to DNA repair processes) and MAEBL-type domain (C-terminus, related to erythrocyte invasion in apicomplexan). This gene showed its highest expression level in metacyclic promastigotes, the infective forms; by fluorescence microscopy assay, we demonstrated the nuclear localization of LmjPES protein. After generating mutant parasites overexpressing <i>LmjPES</i>, we observed that these clones displayed a dramatic increase in the ratio of cell infection within macrophages. Furthermore, BALB/c mice infected with these transgenic parasites exhibited higher footpad inflammation compared to those inoculated with non-overexpressing parasites.https://www.mdpi.com/1422-0067/22/22/12592<i>Leishmania</i>pescadilloPESribosome biogenesisinfection |
| spellingShingle | Miriam Algarabel Celia Fernández-Rubio Katerina Musilova José Peña-Guerrero Andrés Vacas Esther Larrea Paul A. Nguewa In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity International Journal of Molecular Sciences <i>Leishmania</i> pescadillo PES ribosome biogenesis infection |
| title | In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity |
| title_full | In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity |
| title_fullStr | In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity |
| title_full_unstemmed | In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity |
| title_short | In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity |
| title_sort | in i leishmania major i the homolog of the oncogene pes1 may play a critical role in parasite infectivity |
| topic | <i>Leishmania</i> pescadillo PES ribosome biogenesis infection |
| url | https://www.mdpi.com/1422-0067/22/22/12592 |
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