- Malaria Research and Control
- Mosquito-borne diseases and control
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Invertebrate Immune Response Mechanisms
- Toxoplasma gondii Research Studies
- Escherichia coli research studies
- Bone Metabolism and Diseases
- Enzyme Production and Characterization
- Bacterial Genetics and Biotechnology
- Signaling Pathways in Disease
- Vibrio bacteria research studies
- Parasites and Host Interactions
- Trypanosoma species research and implications
- Viral gastroenteritis research and epidemiology
- Natural product bioactivities and synthesis
- Enzyme Structure and Function
- Research on Leishmaniasis Studies
- Biochemical and Structural Characterization
- Metal complexes synthesis and properties
- Ubiquitin and proteasome pathways
- Drug Transport and Resistance Mechanisms
- Aquaculture disease management and microbiota
- RNA and protein synthesis mechanisms
- Complement system in diseases
Institut Pasteur
2010-2019
Immunité et Cancer
2019
National Academies of Sciences, Engineering, and Medicine
1991-2014
Biotechnology Research Institute
2001-2012
National Research Council Canada
1991-2012
Institut de Biologie Moléculaire des Plantes
2009
McGill University
1996-2008
National University of Singapore
2008
Université de Montréal
1980-2007
Bernhard Nocht Institute for Tropical Medicine
2006
A 31-kb fragment of the large virulence plasmid Shigella flexneri is necessary for bacterial entry into epithelial cells in vitro. One locus this encodes IpaA, -B, -C, and -D proteins, which are dominant antigens humoral immune response during shigellosis. To address role ipa genes, clustered an operon, we constructed a selectable cassette that does not affect transcription downstream genes used to inactivate ipaB, ipaC, ipaD genes. Each these nonpolar mutants was defective lysis phagocytic...
Many protozoans of the phylum Apicomplexa are invasive parasites that exhibit a substrate-dependent gliding motility. Plasmodium (malaria) sporozoites, stage parasite invades salivary glands mosquito vector and liver vertebrate host, express surface protein called thrombospondin-related anonymous (TRAP) has homologs in other Apicomplexa. By gene targeting rodent Plasmodium, we demonstrate TRAP is critical for sporozoite infection rat liver, essential motility vitro. This suggests likely...
The merozoite stage of the malaria parasite that infects erythrocytes and causes symptoms disease is initially formed inside host hepatocytes. However, mechanism by which hepatic merozoites reach blood vessels (sinusoids) in liver escape immune system before invading remains unknown. Here, we show parasites induce death detachment their hepatocytes, followed budding parasite-filled vesicles (merosomes) into sinusoid lumen. Parasites simultaneously inhibit exposure phosphatidylserine on outer...
ABSTRACT The severe acute respiratory syndrome coronavirus papain-like protease (SARS-CoV PLpro) is involved in the processing of viral polyprotein and, thereby, contributes to biogenesis virus replication complex. Structural bioinformatics has revealed a relationship for SARS-CoV PLpro herpesvirus-associated ubiquitin-specific (HAUSP), protease, indicating potential deubiquitinating activity addition its function (T. Sulea, H. A. Lindner, E. O. Purisima, and R. Menard, J. Virol. 79:...
Malaria infection starts when the sporozoite stage of Plasmodium parasite is injected into skin by a mosquito. Sporozoites are known to traverse host cells before finally invading hepatocyte and multiplying erythrocyte-infecting forms, but how sporozoites reach hepatocytes in liver role cell traversal (CT) remain unclear. We report first quantitative imaging study rodents. show that can cross sinusoidal barrier multiple mechanisms, targeting Kupffer (KC) or endothelial associated not with CT...
Most Apicomplexan parasites, including the human pathogens Plasmodium, Toxoplasma, and Cryptosporidium, actively invade host cells display gliding motility, both actions powered by parasite microfilaments. In Plasmodium sporozoites, thrombospondin-related anonymous protein (TRAP), a member of group transmembrane proteins that have common adhesion domains, is necessary for motility infection vertebrate host. Here, we provide genetic evidence TRAP directly involved in capping process drives...
Summary Shigella flexneri kills macrophages through apoptosis, involving the induction of host cell DNA fragmentation and characteristic morphological changes. can only cause damage if it escapes from phagolysosome into cytoplasm. The S. cytotoxic genes have been localized to ipa operon shigella's virulence plasmid. ipaB , C D deletion mutants are not invasive therefore cytotoxic. In order distinguish involved in escape as distinct cytotoxicity, we constructed strains that secrete low...
The bacterial pathogen Shigella flexneri causes bacillary dysentery in humans by invading coloncytes. Upon contact with epithelial cells, S. elicits localized plasma membrane projections sustained long actin filaments which engulf the microorganism. products necessary for entry include three secretory proteins: IpaB, IpaC, and IpaD. Extracellular IpaB IpaC associate a soluble complex, Ipa complex. We have immunopurified this complex on latex beads found that they were efficiently...
Summary Genes required for entry of Shigella flexneri into epithelial cells in vitro are clustered two adjacent loci, one which encodes secretory proteins, the IpaA–D and other their dedicated secretion apparatus, Mxi–Spa translocon. Ipa secretion, is induced upon contact bacteria with cells, prevented during growth vitro. Here, we show that ipaB ipaD mutations lead to enhanced a set about 15 proteins. These extracellular proteins some Ipas associate organized structures consisting extended...
Malaria is contracted when Plasmodium sporozoites are inoculated into the vertebrate host during blood meal of a mosquito. In infected mosquitoes, present in large numbers secretory cavities salivary glands at most distal site system. However, how move through system mosquito, both resting and feeding unknown. Here, we observed fluorescent berghei within live Anopheles stephensi mosquitoes their ducts. We show that mosquito by gliding, type motility associated with capacity to invade cells....
The cathepsin L propeptide (phcl-2) was expressed in Saccharomyces cerevisiae using a human procathepsin L/α-factor fusion construct containing stop codon at position −1 (the C-terminal amino acid of the proregion). Since yield after purification very low, also obtained by an alternate procedure through controlled processing inactive mutant (Cys25Ser/Thr110Ala) Pichia pastoris, small amounts L. peptide resulting from cleavage proenzyme (phcl-1) then purified HPLC. propeptides were...
Plasmodium and Toxoplasma are parasites of major medical importance that belong to the Apicomplexa phylum protozoa. These transform into various stages during their life cycle express a specific set proteins at each stage. Although little is yet known how gene expression controlled in Apicomplexa, histone modifications, particularly acetylation, emerging as key regulators parasite differentiation stage conversion. We investigated anti-Apicomplexa effect FR235222, deacetylase inhibitor...
Apicomplexan parasites invade host cells by forming a ring-like junction with the cell surface and actively sliding through inside an intracellular vacuole. Apical membrane antigen 1 is conserved in apicomplexans long-standing malaria vaccine candidate. It considered to have multiple important roles during penetration, primarily structuring interacting rhoptry neck 2 protein transducing force generated parasite motor internalization. Here, we generate Plasmodium sporozoites merozoites...
The first step of Plasmodium development in vertebrates is the transformation sporozoite, parasite stage injected by mosquito skin, into merozoites, that invades erythrocytes and initiates disease. current view that, mammals, this conversion occurs only inside hepatocytes. Here, we document sporozoites rodent-infecting merozoites skin mice. After bite, ∼50% parasites remain at 24 h ∼10% are developing epidermis dermis, as well immunoprivileged hair follicles where they can survive for weeks....
Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in insect salivary glands. Sporozoites only differentiate inside hepatocytes mammalian host. We show that sporozoite latency is an active process controlled a eukaryotic initiation factor-2α (eIF2α) kinase (IK2) and phosphatase. IK2 activity dominant gland sporozoites, leading to inhibition translation accumulation stalled mRNAs into granules. When sporozoites injected host, eIF2α phosphatase...