Members of the mitogen-activated protein (MAP) kinase cascade are important for the establishment of a Leishmania mexicana infection and are involved in flagellar length control, although the underlying molecular mechanisms remain to be elucidated. This study reports the cloning and characterization of LmxPK4, a MAP kinase kinase homologue of L. mexicana displaying putative plant-like regulatory phosphorylation sites. The recombinant protein has autophosphorylating activity and phosphorylates myelin basic protein. An LmxPK4 gene deletion mutant showed a proliferation defect after infection of macrophages and no or delayed lesion development in mice. Irrespective of the onset of lesion development parasites showed an early and homogeneous lesion development in re-infection experiments. This is indicative for a compensation of the null mutant phenotype. Additionally, this phenotype could be reverted by reintroduction of the wild-type gene into the deletion background. Mutants expressing loss-of-function or N-terminally truncated versions of LmxPK4 retained the null mutant phenotype. LmxPK4 is stage-specifically expressed in promastigotes and during differentiation to amastigotes, but is not detectable in amastigotes isolated from the mammalian host. Moreover, its in vitro kinase activity increases with temperature rise up to 40 degrees C. Our results suggest that LmxPK4 is involved in the differentiation process and affects virulence of Leishmania mexicana.
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http://dx.doi.org/10.1111/j.1365-2958.2005.04614.x | DOI Listing |
Chem Biodivers
January 2025
University of Lille: Universite de Lille, UMR BioEcoAgro, 3 rue du Professeur Laguesse, 59800, LILLE, FRANCE.
Parasitic diseases such as trypanosomiasis and leishmaniasis pose significant health challenges in Africa. The Senegalese Pharmacopoeia, known for its many medicinal plants with anti-infectious properties, can be a source of antiparasitic natural products. This study aimed to evaluate the in vitro antiparasitic activities of 33 methanolic extracts from 24 ethnopharmacologically selected plants against Trypanosoma brucei brucei and Leishmania mexicana mexicana, as well as their cytotoxic activities on WI-38 cells.
View Article and Find Full Text PDFFront Parasitol
April 2024
INRS- Centre Armand-Frappier Santé Biotechnologie, Université du Québec, Laval, QC, Canada.
Extracellular vesicles released by the protozoan parasite display immunomodulatory properties towards mammalian immune cells. In this study, we have evaluated the potential of extracellular vesicles derived from the non-pathogenic protozoan towards the development of a vaccine adjuvant. As a proof of concept, we expressed in a codon-optimized SARS-CoV-2 Spike protein fused to the secreted acid phosphatase signal peptide in the N-terminal and to a 6×-His stretch in the C-terminal.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
The ability to determine the essentiality of a gene in the protozoan parasite Leishmania is important to identify potential targets for intervention and understanding the parasite biology. CRISPR gene editing technology has significantly improved gene targeting efficiency in Leishmania. There are two commonly used CRISPR gene targeting methods in Leishmania; the stable expression of the gRNA and Cas9 using a plasmid containing a Leishmania ribosomal RNA gene promoter (rRNA-P stable protocol) and the T7 RNA polymerase based transient gRNA expression system in promastigotes stably expressing Cas9 (T7 transient protocol).
View Article and Find Full Text PDFMol Microbiol
January 2025
Laboratório de Biologia Molecular de Patógenos (LBMP), Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
Leishmania presents a complex life cycle that involves both invertebrate and vertebrate hosts. By regulating gene expression, protein synthesis, and metabolism, the parasite can adapt to various environmental conditions. This regulation occurs mainly at the post-transcriptional level and may involve epitranscriptomic modifications of RNAs.
View Article and Find Full Text PDFNat Commun
January 2025
School of Infection and Immunity, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, UK.
For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L.
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