Leishmania major is the main causative agent of cutaneous leishmaniasis in the Old World. In Leishmania parasites, the lack of transcriptional control is mostly compensated by post-transcriptional mechanisms. Methylation of arginine is a conserved post-translational modification executed by Protein Arginine Methyltransferase (PRMTs). The genome from L. major encodes five PRMT homologs, including the cytosolic protein associated with several RNA-binding proteins, LmjPRMT7. It has been previously reported that LmjPRMT7 could impact parasite infectivity. In addition, a more recent work has clearly shown the importance of LmjPRMT7 in RNA-binding capacity and protein stability of methylation targets, demonstrating the role of this enzyme as an important epigenetic regulator of mRNA metabolism. In this study, we unveil the impact of PRMT7-mediated methylation on parasite development and virulence. Our data reveals that higher levels of LmjPRMT7 can impair parasite pathogenicity, and that deletion of this enzyme rescues the pathogenic phenotype of an attenuated strain of L. major. Interestingly, lesion formation caused by LmjPRMT7 knockout parasites is associated with an exacerbated inflammatory reaction in the tissue correlated with an excessive neutrophil recruitment. Moreover, the absence of LmjPRMT7 also impairs parasite development within the sand fly vector Phlebotomus duboscqi. Finally, a transcriptome analysis shed light onto possible genes affected by depletion of this enzyme. Taken together, this study highlights how post-transcriptional regulation can affect different aspects of the parasite biology.
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http://dx.doi.org/10.1371/journal.pntd.0009230 | DOI Listing |
PLoS Negl Trop Dis
December 2024
Laboratory of Molecular Epidemiology and Experimental Pathology, Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
Background: Cutaneous Leishmaniases (CL), highly endemic in Africa and Mediterranean region, are caused by different Leishmania parasite species. Accurate species identification is crucial for effective diagnosis, treatment, and control of these diseases, but traditionally relies on DNA-based methods. High Resolution Melting analysis PCR (HRM PCR) provides rapid results and precise differentiation based on nucleotide variations.
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December 2024
Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé Environnement Travail), UMR S 1085, Rennes, France.
Background: Leishmaniasis, caused by Leishmania protozoan parasites transmitted by Phlebotomine sand flies, is a significant public health concern in the Mediterranean basin. Effective monitoring of Leishmania-infected sand flies requires standardized tools for comparing their distribution and infection prevalence. Consistent quantitative real-time PCR (qPCR) parameters and efficient DNA extraction protocols are crucial for reliable results over time and across regions.
View Article and Find Full Text PDF3 Biotech
January 2025
Cell and Molecular Biology Laboratory, Department of Zoology, Soban Singh Jeena University, Campus Almora, Almora, Uttarakhand India.
Unlabelled: Visceral leishmaniasis (VL), caused by , remains challenging to treat due to severe side effects and increasing drug resistance associated with current chemotherapies. Our study investigates the anti-leishmanial potential of from Uttarakhand, India, with extracts prepared from leaves and stems using ethanol and hexane. Advanced GC-MS analysis identified over 100 bioactive compounds, which were screened using molecular docking to assess their binding to LdHEL-67, a DDX3-DEAD box RNA helicase of donovani.
View Article and Find Full Text PDFExp Parasitol
December 2024
Centre de Recherche en Infectiologie du Centre de Recherche du CHU de Québec and Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Quebec City, Québec, Canada. Electronic address:
The protozoan parasite Leishmania has a large family of major facilitator membrane proteins part of the Folate Biopterin Transporter (FBT) family. The chromosome 10 of Leishmania has a cluster of 7 FBT genes including the S-Adenosyl methionine (AdoMet) transporter and the functionally characterized folate transporters FT1 and FT5. Six of the 7 FBT proteins coded by this locus are located at the plasma membrane as determined by gene fusions with the green fluorescent protein.
View Article and Find Full Text PDFActa Trop
December 2024
Department of Parasitology, Faculty of Medicine, Ege University, Izmir, Turkey; Department of Basic Oncology, Institute of Health Sciences, Ege University, Izmir, Turkey. Electronic address:
Leishmaniasis is a neglected infectious disease that affects millions of people worldwide. Visceral leishmaniasis (VL) caused by Leishmania infantum and cutaneous leishmaniasis (CL) caused by L. major/ L.
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