A5076302697- Malaria Research and Control
- Mosquito-borne diseases and control
- Plant Pathogenic Bacteria Studies
- Plant-Microbe Interactions and Immunity
- Legume Nitrogen Fixing Symbiosis
- Invertebrate Immune Response Mechanisms
- Trypanosoma species research and implications
- Hemoglobinopathies and Related Disorders
- Toxoplasma gondii Research Studies
- Blood properties and coagulation
- Erythrocyte Function and Pathophysiology
- Venomous Animal Envenomation and Studies
- HIV Research and Treatment
- Sphingolipid Metabolism and Signaling
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- Lipid metabolism and biosynthesis
- Polyamine Metabolism and Applications
- Peroxisome Proliferator-Activated Receptors
- Plant Parasitism and Resistance
- Antibiotics Pharmacokinetics and Efficacy
- Parasites and Host Interactions
- Insect Resistance and Genetics
- Cellular transport and secretion
- CRISPR and Genetic Engineering
Université de Montpellier
2010-2023
Centre National de la Recherche Scientifique
2010-2023
Inserm
2017-2023
Laboratory of Pathogens and Host Immunity
2010-2018
Imperial College London
1999-2000
Institut des Sciences du Végétal
1994-1999
University of Helsinki
1997
Institut für biologische Forschung
1993
Highlights•Two-thirds of Plasmodium berghei genes contribute to normal blood stage growth•The core genome malaria parasites is highly optimized for rapid host colonization•Essential parasite and pathways are identified drug target prioritization•Low functional redundancy reflects the constant environment encountered by a parasiteSummaryThe genomes contain many unknown function. To assist development through identification essential pathways, we have measured competitive growth rates in mice...
hrp genes, basic pathogenicity genes of the pepper and tomato pathogen Xanthomonas campestris pv. vesicatoria, are regulated dependent on environmental conditions. We isolated hrpXv gene, which was found to be outside large cluster comprising six loci hrpA hrpF. The predicted HrpXv protein is 476 amino acids long has a molecular mass 52.5 kDa. HrpX highly conserved among xanthomonads member AraC family regulatory proteins. An insertion mutant typical phenotype no longer allows induction five...
Xanthomonas campestris pv. vesicatoria is the causal agent of bacterial spot disease pepper and tomato plants. Expression its basic pathogenicity genes, hrp induced in planta XVM2 medium dependent on regulatory gene hrpXv for five out six loci 23-kb cluster. Here we describe isolation a novel gene, hrpG, that was identified after chemical mutagenesis located next to gene. In hrpG mutant induction expression seven hrpA hrpF, abolished, suggesting functions at top cascade. only locus encodes...
Studies of essential pathogenicity determinants in Gram-negative bacteria have revealed the conservation type III protein secretion systems that allow delivery virulence factors into host cells from plant and animal pathogens. Ten 21 Hrp proteins pathogen Xanthomonas campestris pv. vesicatoria been suggested to be part a machinery. Here, we report hrp -dependent two avirulence proteins, AvrBs3 AvrRxv, by X. strains constitutively express genes. Secretion occurred without leakage cytoplasmic...
The hrp cluster of the pepper and tomato pathogen Xanthomonas campestris pv. vesicatoria is required for both pathogenicity on susceptible host plants induction hypersensitive reaction resistant plants. hrpA locus located at left end 25-kb region encodes a single 64-kDa Hrp protein, HrpA1, which belongs to PulD superfamily proteins involved in type II III protein secretion. In this study, we developed defined medium without any plant-derived molecules that induces expression vitro....
During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds inhibit phosphatidylcholine biosynthesis de novo choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth the human Plasmodium falciparum and P. vivax was 1000-fold less toxic to mammalian cell lines. A...
hrpG is a key regulatory gene for transcriptional activation of pathogenicity genes (hrp) Xanthomonas campestris pv. vesicatoria. We identified three mutations in which render hrp expression constitutive normally suppressing medium. The result novel amino acid substitutions compared to related proteins, such as OmpR. In addition, mutated enhances the timing and intensity plant reactions infection assays.
Xanthomonas campestris pv. vesicatoria is the causal agent of bacterial spot disease on pepper and tomato plants. We reported previously that main hrp (hypersensitive reaction pathogenicity) gene cluster in X. c . contains six transcription units, designated hrpA to hrpF present here sequence hrpD operon an analysis non‐polar mutants each genes. Three genes, hrcQ , hrcR hrcS are predicted encode conserved components type III protein secretion systems plant mammalian pathogenic bacteria. For...
ABSTRACT Phosphoinositides are important regulators of diverse cellular functions, and phosphatidylinositol 3-monophosphate (PI3P) is a key element in vesicular trafficking processes. During its intraerythrocytic development, the malaria parasite Plasmodium falciparum establishes sophisticated but poorly characterized protein lipid system. Here we established detailed phosphoinositide profile P. -infected erythrocytes found abundant amounts PI3P, while 3,5-bisphosphate was not detected. PI3P...
Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because its essential original metabolic pathways, apicoplast has become target development new anti-apicomplexan drugs. Here we show that lipid phosphatidylinositol 3-monophosphate (PI3P) is involved in biogenesis Toxoplasma gondii. In yeast mammalian cells,...
The urgent need for new antimalarial therapies arises from the alarming spread of malaria parasite resistance to existing drugs. A promising candidate, UA2239, an acyclic nucleoside phosphonate with a guanine as nucleobase, demonstrates rapid and irreversible cytotoxic effects on Plasmodium parasites, both in vitro animal model. It blocks active exit process, named egress, merozoites gametes infected erythrocytes. Interestingly, while mutations cyclic GMP-dependent protein kinase (PKG) were...
Summary Critical events in the life cycle of malaria parasites are controlled by calcium-dependent signalling cascades, yet molecular mechanisms calcium release remain poorly understood. The synchronized development Plasmodium berghei gametocytes relies on rapid from internal stores within 10 s being exposed to mosquito-derived xanthurenic acid (XA). Here we addressed function phosphoinositide-specific phospholipase C (PI-PLC) for regulating gametocyte activation. XA triggered hydrolysis...
The malaria parasite, Plasmodium falciparum, develops and multiplies in the human erythrocyte. It needs to synthesize considerable amounts of phospholipids (PLs), principally phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS). Several metabolic pathways coexist for their de novo biosynthesis, involving a dozen enzymes. Given importance these PLs survival we sought determine sources understand connections dependencies between multiple pathways. We used three...
The fimA gene of Xanthomonas campestris pv. vesicatoria was identified and characterized. A 20-mer degenerate oligonucleotide complementary to the N-terminal amino acid sequence purified 15.5-kDa fimbrillin used locate on a 2.6-kb SalI fragment X. 3240 genome. nucleotide 1.4-kb containing region revealed two open reading frames predicting highly homologous proteins FimA FimB. FimA, which composed 136 acids had calculated molecular weight 14,302, showed high identity type IV precursors. fimB...
Phosphoinositides regulate numerous cellular processes by recruiting cytosolic effector proteins and acting as membrane signalling entities. The metabolism localization of phosphoinositides are tightly regulated distinct lipid kinases phosphatases. Here, we identify characterize a unique phosphatidylinositol 3 kinase (PI3K) in Toxoplasma gondii, protozoan parasite belonging to the phylum Apicomplexa. Conditional depletion this enzyme subsequently its product, PI(3)P, drastically alters...
Malaria parasites alternate between intracellular and extracellular stages successful egress from the host cell is crucial for continuation of life cycle. We investigated Plasmodium berghei gametocytes, an essential process taking place within a few minutes after uptake blood meal by mosquito. Egress entails rupture two membranes surrounding parasite: parasitophorous vacuole membrane (PVM), red (RBCM). High-speed video microscopy 56 events revealed that in both genders comprises four...
An inherited gain-of-function variant (E756del) in the mechanosensitive cationic channel PIEZO1 was shown to confer a significant protection against severe malaria. Here, we demonstrate vitro that human red blood cell (RBC) infection by Plasmodium falciparum is prevented pharmacological activation of PIEZO1. Yoda1 causes an increase intracellular calcium associated with rapid echinocytosis inhibits RBC invasion, without affecting parasite intraerythrocytic growth, division or egress....
Targeting the crucial step of Plasmodium transition from vertebrate host to mosquito vector is a promising approach eliminate malaria. Uptake by activates gametocytes within seconds, and in case male (micro) leads rapid DNA replication release eight flagellated gametes. We developed sensitive assay monitor P. berghei microgametocyte activation based on [3H]hypoxanthine incorporation into DNA. Optimal pH range xanthurenic acid concentrations for gametocyte were established kinetics...
Phosphoinositide-specific phospholipase C (PI-PLC) is a major regulator of calcium-dependent signal transduction, which has been shown to be important in various processes the malaria parasite Plasmodium. PI-PLC generally implicated calcium liberation from intracellular stores through action its product, inositol-(1,4,5)-trisphosphate, and itself dependent on for activation. Here we describe plc genes Plasmodium species. The encoded proteins contain all domains typically found PI-PLCs δ...