A5004980531- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Vibrio bacteria research studies
- CRISPR and Genetic Engineering
- Diagnosis and treatment of tuberculosis
- Protein Structure and Dynamics
- Clostridium difficile and Clostridium perfringens research
- Antimicrobial Resistance in Staphylococcus
- Cancer therapeutics and mechanisms
- Bacteriophages and microbial interactions
- Bacterial biofilms and quorum sensing
- Natural product bioactivities and synthesis
- Pneumocystis jirovecii pneumonia detection and treatment
- Protein Kinase Regulation and GTPase Signaling
- Phosphorus compounds and reactions
- Inhalation and Respiratory Drug Delivery
- Advanced NMR Techniques and Applications
- Pancreatic function and diabetes
- Agriculture and Biological Studies
- Synthesis and Reactivity of Sulfur-Containing Compounds
Inserm
2015-2024
Centre National de la Recherche Scientifique
2015-2024
Université de Montpellier
2015-2024
Centre de Biologie Structurale
2015-2024
Centre Hospitalier Universitaire de Nîmes
2021
Biolog (United States)
2021
Centre Hospitalier Universitaire de Montpellier
2021
Centre de Biologie du Développement
2021
Birkbeck, University of London
2003-2014
University College London
2005
Although agonists bind directly in the heptahelical domain (HD) of most class-I rhodopsin-like G protein coupled receptors (GPCRs), class-III extracellular their receptors. Indeed, latter possess a large composed cysteine-rich and Venus flytrap module. Both low sequence homology structural organization GPCRs raised question whether or not HD these functions same way as GPCRs. Here, we show that metabotropic glutamate receptor 5 (mGlu(5)) displays agonist-independent constitutive activity...
Chromatin insulators are genetic elements implicated in the organization of chromatin and regulation transcription. In Drosophila, different insulator types were characterized by their locus-specific composition proteins co-factors. Insulators mediate specific long-range DNA contacts required for three dimensional interphase nucleus transcription regulation, but mechanisms underlying formation these is currently unknown. Here, we investigate molecular associations between components...
Culex pipiens mosquitoes are infected with Wolbachia (wPip) that cause an important diversity of cytoplasmic incompatibilities (CIs). Functional transgenic studies have implicated the cidA-cidB operon from wPip and its homolog in wMel CI between Drosophila males uninfected females. However, genetic basis induced by different strains was unknown. We show here remarkable C. complex is due to presence, all tested genomes, several copies operon, which undergoes diversification through...
Engineered bacteria promise to revolutionize diagnostics and therapeutics, yet many applications are precluded by the limited number of detectable signals. Here we present a general framework engineer synthetic receptors enabling bacterial cells respond novel ligands. These activated via ligand-induced dimerization single-domain antibody fused monomeric DNA-binding domains (split-DBDs). Using E. coli as model system, both transmembrane cytosolic using VHH for ligand detection demonstrate...
Tuberculosis claims >1 million lives annually, and its causative agent Mycobacterium tuberculosis is a highly successful pathogen. Protein kinase B (PknB) reported to be critical for mycobacterial growth. Here, we demonstrate that PknB-depleted M. can replicate normally synthesize peptidoglycan in an osmoprotective medium. Comparative phosphoproteomics of PknB-producing mycobacteria identify CwlM, essential regulator synthesis, as major PknB substrate. Our complementation studies cwlM mutant...
Abstract Bacterial biosensors, or bactosensors, are promising agents for medical and environmental diagnostics. However, the lack of scalable frameworks to systematically program ligand detection limits their applications. Here we show how novel, clinically relevant sensing modalities can be introduced into bactosensors in a modular fashion. To do so, have leveraged synthetic receptor platform, termed EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) which...
Mycolic acids are key cell wall components for the survival, pathogenicity, and antibiotic resistance of human tubercle bacillus. Although it was thought that Mycobacterium tuberculosis tightly regulates their production to adapt prevailing environmental conditions, molecular mechanisms governing mycolic acid biosynthesis remained extremely obscure. Meromycolic acids, direct precursors synthesized by a type II fatty synthase from acyl carrier protein-bound substrates extended iteratively,...
The use of linear DNA templates in cell-free systems promises to accelerate the prototyping and engineering synthetic gene circuits. A key challenge is that are rapidly degraded by exonucleases present cell extracts. Current approaches tackle problem adding exonuclease inhibitors DNA-binding proteins protect DNA, requiring additional time- resource-intensive steps. Here, we delete recBCD cluster from Escherichia coli BL21 genome. We show resulting systems, with buffers optimized specifically...
Although Mycobacterium tuberculosis (M. tb) comprises 11 serine/threonine protein kinases, the mechanisms of regulation these kinases and nature their endogenous substrates remain largely unknown. Herein, we characterized M. tb kinase PknL by demonstrating that it expresses autophosphorylation activity phosphorylates Rv2175c. On-target dephosphorylation/MALDI-TOF for identification phosphorylated peptides was used in combination with LC-ESI/MS/MS localization phosphorylation sites. By doing...
Host metabolism reprogramming is a key feature of Mycobacterium tuberculosis (
ABSTRACT The first-line specific antituberculous drug isoniazid inhibits the fatty acid elongation system (FAS) FAS-II involved in biosynthesis of mycolic acids, which are major lipids mycobacterial envelope. MabA protein that catalyzes second step cycle is structurally and functionally related to vivo target isoniazid, InhA, an NADH-dependent enoyl-acyl carrier reductase. present work shows NADPH-dependent β-ketoacyl reduction activity efficiently inhibited by vitro a mechanism similar InhA...
Recent efforts have underlined the role of serine/threonine protein kinases in growth, pathogenesis, and cell wall metabolism Mycobacterium tuberculosis. Although most been investigated for their physiological roles, little information is available regarding how kinase-dependent phosphorylation regulates activity kinase substrates. Herein, we focused on M. tuberculosis Rv2175c, a unknown function, conserved actinomycetes, recently identified as substrate PknL kinase. We solved solution...
Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. and ParA are key components of bacterial chromosome segregation apparatus. a cytosolic conserved binds specifically to centromere-like DNA parS sequences interacts with ParA, weak ATPase required its proper localization. Mass spectrometry identified presence ten phosphate groups, thus indicating on eight threonines, Thr32, Thr41, Thr53, Thr110,...
PknB is an essential serine/threonine protein kinase required for mycobacterial cell division and cell-wall biosynthesis. Here we demonstrate that overexpression of the external PknB_PASTA domain in mycobacteria results delayed regrowth, accumulation elongated bacteria increased sensitivity to β-lactam antibiotics. These changes are accompanied by altered production certain enzymes involved biosynthesis as revealed proteomics studies. The growth inhibition caused completely abolished...
Abstract Chemically-induced dimerization (CID) systems are essential tools to interrogate and control biological systems. AcVHH is a single domain antibody homo-dimerizing upon caffeine binding. has strong potential for clinical applications through caffeine-mediated in vivo of therapeutic gene networks. Here we provide the structural basis caffeine-induced homo-dimerization acVHH.