A5080222404- Legionella and Acanthamoeba research
- Vibrio bacteria research studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Toxoplasma gondii Research Studies
- Vector-borne infectious diseases
- Neonatal Health and Biochemistry
- Bacterial Genetics and Biotechnology
- Autophagy in Disease and Therapy
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- Bacterial biofilms and quorum sensing
- Mosquito-borne diseases and control
- Antibiotic Resistance in Bacteria
- Immune Response and Inflammation
- Inflammasome and immune disorders
- Cellular transport and secretion
- Biomedical Research and Pathophysiology
- Cytomegalovirus and herpesvirus research
- Enzyme Structure and Function
- Cancer Research and Treatments
- interferon and immune responses
- Yersinia bacterium, plague, ectoparasites research
- Calcium signaling and nucleotide metabolism
- Erythrocyte Function and Pathophysiology
Yale University
2016-2025
IE University
2020
University School
2020
Clinique Vétérinaire Benjamin Franklin
2014
Laboratoire d'Enzymologie et Biochimie Structurales
2013
Centre National de la Recherche Scientifique
2013
Emory University
2004
Max Planck Institute of Biophysics
2003
DKFZ-ZMBH Alliance
2000
German Cancer Research Center
2000
The intracellular pathogen Legionella pneumophila subverts vesicle traffic in eukaryotic host cells to create a vacuole that supports replication. dot/icm genes encode protein secretion apparatus L. require for biogenesis of this vacuole. Here we show produce called RalF functions as an exchange factor the ADP ribosylation (ARF) family guanosine triphosphatases (GTPases). is required localization ARF on phagosomes containing . Translocation through phagosomal membrane -dependent process....
Macrophages from C57BL/6J (B6) mice restrict growth of the intracellular bacterial pathogen Legionella pneumophila. Restriction requires caspase-1 and leucine-rich repeat-containing protein Naip5 (Birc1e). We identified mutants L. pneumophila that evade macrophage innate immunity. All were deficient in expression flagellin, primary flagellar subunit, failed to induce caspase-1-mediated death. Interestingly, a previously isolated mutant (fliI) expresses, but does not assemble, flagellin did...
Axing Autophagy When intracellular pathogens like Legionella pneumophila take up residence in mammalian host cells, they must combat the efforts of cell to attack them. is a process by which cells digest their own constituents, often involved response starvation or pathogen attack. Choy et al. (p. 1072 , published online 25 October) now describe how L. can inhibit autophagy pathway eukaryotic and provide detailed description biochemical mechanism. A effector protein, RavZ, acts as very...
Specialized secretion systems are used by many bacteria to deliver effector proteins into host cells that can either mimic or disrupt the function of eukaryotic factors. We found intracellular pathogens Legionella pneumophila and Coxiella burnetii use a type IV system large number different bacterial containing ankyrin repeat homology domains called Anks. The L. AnkX protein prevented microtubule-dependent vesicular transport interfere with fusion -containing vacuole late endosomes after...
A flagellin-independent caspase-1 activation pathway that does not require NAIP5 or NRLC4 is induced by the intracellular pathogen Legionella pneumophila . Here we demonstrate this requires caspase-11. Treatment of macrophages with LPS up-regulated host components required for caspase-11 pathway. Activation differed from using previously described agonists in was rapid and bacteria a functional type IV secretion system called Dot/Icm. pyroptosis mechanism independent NAIP/NLRC4 axis....
Coxiella burnetii, the causative agent of human Q fever, is an intracellular pathogen that replicates in acidified vacuole derived from host lysosomal network. This encodes a Dot/Icm type IV secretion system delivers bacterial proteins called effectors to cytosol. To identify new effector proteins, functionally analogous Legionella pneumophila was used genetic screen fragments C. burnetii genomic DNA when fused adenylate cyclase reporter were capable directing Dot/Icm-dependent translocation...
Numerous intracellular bacterial pathogens modulate the nature of membrane‐bound compartment in which they reside, although little is known about molecular basis for this control. Legionella pneumophila a pathogen able to grow within human alveolar macrophages and residing phagosome that does not fuse with lysosomes. This study demonstrates dotA product required regulate trafficking L. phagosome. Phagosomes containing + bacteria exhibited differential profiles when compared isogenic mutants....
Within five minutes of macrophage infection by Legionella pneumophila, the bacterium responsible for Legionnaires’ disease, elements rough endoplasmic reticulum (RER) and mitochondria attach to surface bacteria-enclosed phagosome. Connecting these abutting membranes are tiny hairs, which frequently periodic like rungs a ladder. These connections stable high affinity - phagosomes from infected macrophages remain connected ER (as they were in situ) even after homogenized. Thin sections through...
The bvg locus of Bordetella pertussis is required for coordinate regulation several factors associated with virulence. control system modulated by various environmental signals, including low temperature, MgSO4, and nicotinic acid. nucleotide sequence the region has been determined three open reading frames, bvgA, bvgB, bvgC, are present. Twelve-base-pair linker insertion mutations in any these frames result a Bvg- phenotype. predicted protein products bvgA bvgC share homology family...
Legionella pneumophila is a bacterial pathogen that infects eukaryotic host cells and replicates inside specialized organelle morphologically similar to the endoplasmic reticulum (ER). To better understand molecular mechanisms governing transport of Legionella-containing vacuole (LCV), we have identified proteins participate in conversion LCV into replicative organelle. Our data show Rab1 recruited within minutes uptake. recruitment precedes remodeling this compartment by ER-derived...
The Legionella pneumophila Dot/Icm system is a type IV secretion apparatus that transfers bacterial proteins into eukaryotic host cells. RalF protein substrate engaged and translocated cells by the system. In this study, mechanism of Dot/Icm-mediated translocation has been investigated. It was determined occurs before internalization. Sequences essential for were located at C terminus protein. A fusion consisting 20-aa C-terminal peptide appended to calmodulin-dependent adenylate cyclase...
ABSTRACT Caspase-1 activation is a key feature of the innate immune response macrophages elicited by pathogens and variety toxins. Here, we determined requirement for different adapter proteins involved in regulating host processes mediated caspase-1 after macrophage infection Legionella pneumophila . The protein Asc was found to be important during L. infection. Activation through did not require flagellin-sensing pathway involving nucleotide-binding domain leucine-rich repeat-containing...
Coxiella burnetii is an intracellular pathogen that replicates in a lysosome-derived vacuole. The molecular mechanisms used by this bacterium to create pathogen-occupied vacuole remain largely unknown. Here, we conducted visual screen on arrayed library of C. NMII transposon insertion mutants identify genes required for biogenesis mature Coxiella-containing (CCV). Mutants defective Dot/Icm secretion system function or the PmrAB regulatory were incapable replication. Several with growth...
Coxiella burnetii and Legionella pneumophila are evolutionarily related pathogens with different intracellular infection strategies. C. persists within is transmitted by mammalian hosts, whereas, L. found primarily in the environment associated protozoan hosts. Although a type IV secretion system encoded defect organelle trafficking ( dot ) multiplication icm genes virulence determinant that remains highly conserved both bacteria, two encode array of effector proteins delivered into host...