Back to Search
Start Over
In Leishmania major , the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Nov 22; Vol. 22 (22). Date of Electronic Publication: 2021 Nov 22. - Publication Year :
- 2021
-
Abstract
- Leishmaniasis is a neglected tropical disease caused by Leishmania 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 PES1 in Leishmania major ( LmjPES ). 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 LmjPES 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 LmjPES , 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.
- Subjects :
- Animals
Conserved Sequence genetics
Humans
Leishmania major pathogenicity
Leishmaniasis parasitology
Macrophages metabolism
Macrophages parasitology
Mice
Mice, Inbred BALB C
Parasitic Diseases parasitology
RNA-Binding Proteins genetics
Leishmania major genetics
Leishmaniasis genetics
Parasitic Diseases genetics
Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34830469
- Full Text :
- https://doi.org/10.3390/ijms222212592