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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Miriam Algarabel, Celia Fernández-Rubio, Katerina Musilova, José Peña-Guerrero, Andrés Vacas, Esther Larrea, Paul A. Nguewa
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Leishmania</i> pescadillo PES ribosome biogenesis infection Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/82c3ee98cb5044c4b6784b143f716244
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:82c3ee98cb5044c4b6784b143f716244
record_format	dspace
spelling	oai:doaj.org-article:82c3ee98cb5044c4b6784b143f7162442021-11-25T17:58:07ZIn <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity10.3390/ijms2222125921422-00671661-6596https://doaj.org/article/82c3ee98cb5044c4b6784b143f7162442021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12592https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Leishmaniasis 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.Miriam AlgarabelCelia Fernández-RubioKaterina MusilovaJosé Peña-GuerreroAndrés VacasEsther LarreaPaul A. NguewaMDPI AGarticle<i>Leishmania</i>pescadilloPESribosome biogenesisinfectionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12592, p 12592 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Leishmania</i> pescadillo PES ribosome biogenesis infection Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	<i>Leishmania</i> pescadillo PES ribosome biogenesis infection Biology (General) QH301-705.5 Chemistry QD1-999 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
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.
format	article
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
title	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_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_sort	in <i>leishmania major</i>, the homolog of the oncogene pes1 may play a critical role in parasite infectivity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/82c3ee98cb5044c4b6784b143f716244
work_keys_str_mv	AT miriamalgarabel inileishmaniamajorithehomologoftheoncogenepes1mayplayacriticalroleinparasiteinfectivity AT celiafernandezrubio inileishmaniamajorithehomologoftheoncogenepes1mayplayacriticalroleinparasiteinfectivity AT katerinamusilova inileishmaniamajorithehomologoftheoncogenepes1mayplayacriticalroleinparasiteinfectivity AT josepenaguerrero inileishmaniamajorithehomologoftheoncogenepes1mayplayacriticalroleinparasiteinfectivity AT andresvacas inileishmaniamajorithehomologoftheoncogenepes1mayplayacriticalroleinparasiteinfectivity AT estherlarrea inileishmaniamajorithehomologoftheoncogenepes1mayplayacriticalroleinparasiteinfectivity AT paulanguewa inileishmaniamajorithehomologoftheoncogenepes1mayplayacriticalroleinparasiteinfectivity
_version_	1718411813420269568

In <i>Leishmania major</i>, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity

Ejemplares similares