A5091504371- Bacterial Infections and Vaccines
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Protein Structure and Dynamics
- Bacillus and Francisella bacterial research
- Computational Drug Discovery Methods
- Clostridium difficile and Clostridium perfringens research
- Mass Spectrometry Techniques and Applications
- Escherichia coli research studies
- Toxin Mechanisms and Immunotoxins
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Pharmacological Effects of Natural Compounds
- Protein Kinase Regulation and GTPase Signaling
- Antimicrobial Resistance in Staphylococcus
- Synthesis and biological activity
- Ion channel regulation and function
- Environmental Toxicology and Ecotoxicology
- Photoreceptor and optogenetics research
Institut Pasteur
2019-2023
Centre National de la Recherche Scientifique
2019-2023
Université Paris Cité
2020-2023
Sorbonne Paris Cité
2020-2022
Universität Ulm
2016-2019
Calmodulin (CaM) is an evolutionarily conserved eukaryotic multifunctional protein that functions as the major sensor of intracellular calcium signaling. Its calcium-modulated function regulates activity numerous effector proteins involved in a variety physiological processes diverse organs, from proliferation and apoptosis, to memory immune responses. Due pleiotropic roles CaM normal pathological cell functions, antagonists are needed for fundamental studies well potential therapeutic...
Abstract The molecular mechanisms and forces involved in the translocation of bacterial toxins into host cells are still a matter intense research. adenylate cyclase (CyaA) toxin from Bordetella pertussis displays unique intoxication pathway which its catalytic domain is directly translocated across target cell membranes. CyaA region contains segment, P454 (residues 454–484), exhibits membrane‐active properties related to antimicrobial peptides. Herein, results show that this peptide able...
The antibiotic bacitracin (Bac) inhibits cell wall synthesis of gram-positive bacteria. Here, we discovered a totally different activity Bac: the neutralization bacterial exotoxins. Bac prevented intoxication mammalian cells with binary enterotoxins Clostridium botulinum C2, C. perfringens ɩ, difficile transferase (CDT), and Bacillus anihracis lethal toxin. transport (B) subunits these toxins deliver their respective enzyme (A) into cells. Following endocytosis, B form pores in membranes...
The pathogenic bacteria Clostridium difficile, perfringens and botulinum produce the binary actin ADP-ribosylating toxins CDT, iota C2, respectively. These are composed of a transport component (B) separate enzyme (A). When both components assemble on surface mammalian target cells, B mediate entry A via endosomes into cytosol. Here, ADP-ribosylate G-actin, resulting in depolymerization F-actin, cell-rounding eventually death. In present study, we demonstrate that 4-bromobenzaldehyde...
Amphitropic proteins and peptides reversibly partition from solution to membrane, a key process that regulates their functions. Experimental approaches classically used measure protein partitioning into lipid bilayers, such as fluorescence circular dichroism, are hardly usable when the or do not exhibit significant polarity and/or conformational changes upon membrane binding. Here, we describe binding vesicles (B2LiVe), simple, robust, widely applicable nuclear magnetic resonance (NMR)...
The adenylate cyclase (CyaA) toxin produced in Bordetella pertussis is the causative agent of whooping cough. CyaA exhibits remarkable capacity to translocate its N-terminal adenyl domain (ACD) directly across plasma membrane into cytosol eukaryotic cells. Once translocated, calmodulin binds and activates ACD, leading a burst cAMP that intoxicates target cell. Previously, Gonzalez-Bullon et al. reported phospholipase A activity could destabilize facilitate ACD translocation. However, Bumba...
Various bacterial pathogens are producing toxins that target the cyclic Nucleotide Monophosphate (cNMPs) signaling pathways in order to facilitate host colonization. Among them, several exhibiting potent nucleotidyl cyclase activities activated by eukaryotic factors, such as adenylate (AC) toxin, CyaA, from Bordetella pertussis or edema factor, EF, Bacillus anthracis. The characterization of these frequently requires accurate measurements their enzymatic activity vitro, particular for...
Abstract The molecular mechanisms and forces involved in the translocation of bacterial toxins into host cells have thus far remained elusive. adenylate cyclase (CyaA) toxin from Bordetella pertussis displays a unique intoxication pathway which its catalytic domain is directly translocated across target cell membranes. We previously identified region CyaA that contains segment, P454 (residues 454–484), exhibiting membrane-active properties related to antimicrobial peptides. Herein, we show...
Abstract Calmodulin (CaM) is a eukaryotic multifunctional, calcium-modulated protein that regulates the activity of numerous effector proteins involved in variety physiological processes. Calmidazolium (CDZ) potent small molecule antagonist CaM and one most widely used inhibitors cell biology. Here, we report structural characterization CaM:CDZ complexes using combined SAXS, X-ray crystallography, HDX-MS NMR approaches. Our results provide molecular insights into CDZ-induced dynamics changes...
Summary Amphitropic proteins and peptides reversibly partition from solution to membrane, a key process that regulates their functions. Experimental approaches, such as fluorescence circular dichroism, are classically used measure the partitioning of amphitropic into lipid bilayers, yet hardly usable when or do not exhibit significant polarity and/or conformational changes upon membrane binding. Here, we describe B2LiVe ( i . e ., Binding Lipid Vesicles), simple, robust, widely applicable...