A5030845602- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Toxin Mechanisms and Immunotoxins
- Microtubule and mitosis dynamics
- Enzyme function and inhibition
- Signaling Pathways in Disease
- Cellular transport and secretion
- Parasites and Host Interactions
- Alkaline Phosphatase Research Studies
- Agriculture and Rural Development Research
- Indigenous Studies and Ecology
- Melanoma and MAPK Pathways
- Heat shock proteins research
- Rangeland Management and Livestock Ecology
- Lysosomal Storage Disorders Research
- RNA regulation and disease
- Complement system in diseases
- Connexins and lens biology
- Protist diversity and phylogeny
- Photosynthetic Processes and Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Inhalation and Respiratory Drug Delivery
- Renal Diseases and Glomerulopathies
- Synthesis and biological activity
- T-cell and Retrovirus Studies
University of Strathclyde
2008-2023
Bernhard Nocht Institute for Tropical Medicine
2003-2007
In-Q-Tel
2005
Association for Jewish Studies
2005
Max Planck Institute for Biology
1993-2000
Max Planck Society
1995
University of Rochester
1982
Amino acid sensing is an intracellular function that supports nutrient homeostasis, largely through controlled release of amino acids from lysosomal pools. The pathogen Leishmania resides and proliferates within human macrophage phagolysosomes. Here we describe a new pathway in specifically senses the extracellular levels arginine, essential for parasite. During infection, arginine pool depleted due to its use produce metabolites (NO polyamines) constitute part host defense response...
Components of mitogen-activated signal transduction pathways have been shown to be involved in flagellum biogenesis and maintenance. A protein kinase homologue, designated LmxMPK9 from Leishmania mexicana, has recently identified a homology screen its mRNA found present all life stages. Three different splice-addition sites were used for maturation trans-splicing the However, here we show that is exclusively promastigote stage. Recombinant expression Escherichia coli assays revealed...
A striking difference of the life stages protozoan parasite Leishmania is a long flagellum in insect stage promastigotes and rudimentary organelle mammalian amastigotes. LmxMKK, mitogen-activated protein (MAP) kinase from mexicana, required for growth full-length flagellum. We identified LmxMPK3, MAP homologue, with similar expression pattern as LmxMKK being not detectable amastigotes, up-regulated during differentiation to promastigotes, constantly expressed shut down LmxMPK3 null mutants...
Leishmania major aquaglyceroporin (LmjAQP1) adventitiously facilitates the uptake of antimonite [Sb(III)], an active form Pentostam® or Glucantime®, which are first line defence against all forms leishmaniasis. The present paper shows that LmjAQP1 activity is modulated by mitogen-activated protein kinase, LmjMPK2. parasites coexpressing and LmjMPK2 show increased Sb(III) sensitivity. When subjected to a hypo-osmotic stress, these cells faster volume recovery than expressing alone....
ABSTRACT The cellular distribution of two glycosyl-phosphatidylinositol (GPI)-anchored proteins and a trans-membrane protein the compartments involved in their trafficking were investigated insect stage Leishmania mexicana, which belongs to phylogenetically old protozoan family Trypanosomatidae. Electron microscopy sections from high-pressure frozen freeze-substituted cells allowed detailed description exo- endocytic structures located vesicle-rich, densly packed anterior part spindle-shaped...
ABSTRACT During its life cycle, the parasitic protozoon Leishmania mexicana differentiates from a flagellated form, promastigote, to an amastigote form carrying rudimentary flagellum. Besides biochemical changes, this process involves change in overall cell morphology including flagellar shortening. A mitogen-activated protein kinase homologue designated LmxMKK was identified homology screening and found be critically involved regulation of assembly size. is exclusively expressed...
Considering the high incidence of galactofuranose (Gal(f)) in pathogens and its absence from higher eukaryotes, enzymes involved biosynthesis this unusual monosaccharide appear as attractive drug targets. However, although importance Gal(f) bacterial survival or pathogenesis is established, role eukaryotic still undefined. Recently, we reported identification characterization first UDP-galactopyranose mutases. This enzyme holds a central metabolism by providing UDP-Gal(f) to all...
Abstract Leishmania parasites are thought to control protein activity at the post-translational level, e.g. by phosphorylation. In pathogenic amastigote, mammalian stage of parasites, heat shock proteins show increased phosphorylation, indicating a role in stage-specific signal transduction. Here we investigate impact phosphosites L . donovani 90. Using chemical knock-down/genetic complementation approach, mutated 11 confirmed or presumed phosphorylation sites and assessed on overall...
Leishmania promastigotes, the stage of parasite characteristic for sandfly vector, express an abundant glycoconjugate, called lipophosphoglycan, at their surface. Lipophosphoglycan consists lysoalkyl‐ sn ‐glycerophosphoinositol linked to a phosphosaccharide core conserved in all species, which is connected PO 4 ‐6Galβ1,4Manα1 repeats with species‐specific substitutions Gal residue; are capped by and oligosaccharides. Most species also secrete acid phosphatase, which, mexicana , filamentous...
Summary Members of the mitogen‐activated protein (MAP) kinase cascade are important for establishment a Leishmania mexicana infection and involved in flagellar length control, although underlying molecular mechanisms remain to be elucidated. This study reports cloning characterization LmxPK4, MAP homologue L. displaying putative plant‐like regulatory phosphorylation sites . The recombinant has autophosphorylating activity phosphorylates myelin basic protein. An LmxPK4 gene deletion mutant...
Leishmania parasites undergo profound morphological and biochemical changes while passing through their life cycle. Protein kinases have been shown to be involved in the differentiation from extracellular flagellated promastigotes intracellular "non-flagellated" amastigotes vice versa. Moreover, these enzymes are likely regulation of proliferation different stages.Here, we characterize LmxMPK4, a mitogen-activated protein (MAP) kinase homologue mexicana. The reveals all sequence motifs for...
ABSTRACT A mixture of well-defined recombinant antigens together with an adjuvant that preferentially stimulates specific gamma interferon (IFN-γ)-secreting helper type 1 CD4 + T cells (Th1 cells) presents a rational option for vaccine against leishmaniasis. The potential this approach was investigated in murine infections Leishmania mexicana , which are characterized by the absence parasite-specific Th1 response and uncontrolled parasite proliferation. three (glycoprotein 63, cysteine...
Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in host environment and trigger adaptive stage differentiation essential for cell infection. The underlying parasite development remain largely elusive even though mitogen-activated protein kinases (MAPKs) been linked previously to environmentally induced virulence. Here, we unravel highly unusual regulatory MAP kinase 10 (MPK10). Using a transgenic approach, demonstrate MPK10 is...
During its life cycle, the protozoan pathogen Leishmania donovani is exposed to contrasting environments inside insect vector and vertebrate host, which parasite must adapt for extra- intracellular survival. Combining null mutant analysis with phosphorylation site-specific mutagenesis functional complementation we genetically tested requirement of L. chaperone cyclophilin 40 (LdCyP40) infection. Targeted replacement LdCyP40 had no effect on viability, axenic amastigote differentiation,...
Leishmania are protozoan parasites which invade mammalian macrophages and multiply as amastigotes in phagolysosomes (parasitophorous vacuoles). Using L. mexicana bone marrow-derived (BMM), the question is addressed whether infected BMM induced to express major histocompatibility complex class II molecules can present defined antigens specific T helper type 1 cells. As a model antigen, membrane-bound acid phosphatase (MAP), minor protein associated with intracellular vesicles amastigotes, was...
The nucleotide sugar UDP-galactose (UDP-Gal) is essential for the biosynthesis of several abundant glycoconjugates forming surface glycocalyx protozoan parasite Leishmania major. Current data suggest that UDP-Gal could arise de novo by epimerization UDP-glucose (UDP-Glc) or a salvage pathway involving phosphorylation Gal and action UDP-glucose:α-d-galactose-1-phosphate uridylyltransferase as described Leloir. Since both pathways require UDP-Glc, inactivation pyrophosphorylase (UGP)...