A5075142026- Clostridium difficile and Clostridium perfringens research
- Bacterial Genetics and Biotechnology
- Genomics and Phylogenetic Studies
- Glycosylation and Glycoproteins Research
- Gut microbiota and health
- Pharmacological Effects of Natural Compounds
- Nosocomial Infections in ICU
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- Helicobacter pylori-related gastroenterology studies
- Angiogenesis and VEGF in Cancer
- Advanced biosensing and bioanalysis techniques
- Botulinum Toxin and Related Neurological Disorders
- Gastrointestinal motility and disorders
- Protein Structure and Dynamics
- Hemoglobin structure and function
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Enzyme Production and Characterization
- Protist diversity and phylogeny
- Cerebrovascular and Carotid Artery Diseases
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Infant Nutrition and Health
- Carbohydrate Chemistry and Synthesis
Centre National de la Recherche Scientifique
2020-2024
Institut Pasteur
2016-2024
Université Paris Cité
2016-2024
University of Geneva
2020-2024
Inserm
2023-2024
Sorbonne Université
2023-2024
Centre de Recherche des Cordeliers
2023-2024
University of Freiburg
2020
Sorbonne Paris Cité
2016-2019
Délégation Paris 7
2016-2018
Unraveling the mechanism of action and molecular target small molecules remains a major challenge in drug discovery. While many cancer drugs genetic vulnerabilities, loss-of-function screens fail to identify essential genes action. Here, we report CRISPRres, CRISPR-Cas-based screening approach rapidly derive resistance mutations genes. It exploits local variation created by CRISPR-Cas-induced non-homologous end-joining (NHEJ) repair generate wide variety functional in-frame mutations. Using...
Summary Clostridium difficile is a major cause of diarrhoea associated with antibiotherapy. Exposed to stresses in the gut, C. can survive by inducing protection, detoxification and repair systems. In several firmicutes, most these systems are controlled general stress response involving σ B . this work, we studied role physiopathology We showed that survival sigB mutant during stationary phase was reduced. Using transcriptome analysis, controls expression ∼25% genes including involved...
Clostridium difficile, a major human enteropathogen, must cope with foreign DNA invaders and multiple stress factors inside the host. We have recently provided an experimental evidence of defensive function C. difficile CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system important for its survival within phage-rich gut communities. Here, we describe identification type I toxin–antitoxin (TA) systems first functional antisense RNAs in this...
The strict anaerobe Clostridium difficile is the most common cause of nosocomial diarrhea, and oxygen-resistant spores that it forms have a central role in infectious cycle. late stages sporulation require mother cell regulatory protein σK. In Bacillus subtilis, onset σK activity requires both excision prophage-like element (skinBs) inserted sigK gene proteolytical removal an inhibitory pro-sequence. Importantly, rearrangement restricted to because skinBs recombinase produced specifically...
, the major cause of antibiotic-associated diarrhea, is a strict anaerobic, sporulating Firmicutes. However, during its infectious cycle, this anaerobe exposed to low oxygen (O
Clostridium difficile is the main cause of antibiotic-associated diarrhoea. Inside gut, C. must adapt to stresses it copes with, by inducing protection, detoxification and repair systems that belong general stress response involving σB . Following stresses, activation requires a PP2C phosphatase dephosphorylate anti-anti-sigma factor RsbV allows its interaction with anti-sigma RsbW release In this work, we studied signalling pathway responsible for in difficile. Contrary other firmicutes,...
Clostridioides difficile is a major cause of diarrhea associated with antibiotherapy. After germination C. spores in the small intestine, vegetative cells are exposed to low oxygen (O2) tensions. While considered strictly anaerobic, able grow nonstrict anaerobic conditions (1 3% O2) and tolerates brief air exposure indicating that this bacterium harbors an arsenal proteins involved O2 detoxification and/or protection. Tolerance tensions requires presence alternative sigma factor, σB, general...
How specificity is programmed into post-translational modification of proteins by glycosylation poorly understood, especially for O-linked systems. Here we reconstitute and dissect the substrate underpinning cytoplasmic O-glycosylation pathway that modifies all six flagellins, five structural one regulatory paralog, in
Unidirectional growth of filamentous protein assemblies including the bacterial flagellum relies on dedicated polymerization factors (PFs). The molecular determinants and structural transitions imposed by PFs multi-subunit assembly are poorly understood. Here, we unveil FlaY from polarized α-proteobacterium Caulobacter crescentus as a defining member an alternative class specialized flagellin PFs. Unlike paradigmatic FliD capping protein, funnel-like β-propeller fold for polymerization....
SpoIIE is a phosphatase involved in the activation of first sigma factor forespore, σF, during sporulation. A ΔspoIIE mutant Clostridium beijerinckii NCIMB 8052, previously generated by CRISPR-Cas9, did not sporulate but still produced granulose and solvents. Microscopy analysis also showed that cells are elongated with presence multiple septa. This observation suggests C. beijerinckii, necessary for completion sporulation process, as seen Bacillus acetobutylicum. Moreover, when grown...
Many bacteria glycosylate flagellin on serine or threonine residues using pseudaminic acid (Pse) other sialic acid-like donor sugars. Successful reconstitution of Pse-dependent sialylation by the conserved Maf-type glycosyltransferase (fGT) may require (a) missing component(s). Here, we characterize both Maf paralogs in Gram-negative bacterium Shewanella oneidensis MR-1 and reconstitute glycosylation heterologous hosts. Remarkably, uncovered distinct acceptor determinants target...
ABSTRACT Many bacteria decorate flagellin with sialic acid-like sugars such as pseudaminic acid (Pse) by O-glycosylation on serine or threonine residues. Evidence for sufficiency of sialylation a conserved glycosyltransferase (fGT) system is lacking, presumably because (a) missing component(s). Here, we reconstituted two Maf-type fGTs from the Gram-negative bacterium Shewanella oneidensis MR-1 in heterologous host producing Pse donor sugar. While Maf-1 sufficient glycosylation, Maf-2...
Summary Glycosylation of surface structures diversifies cells chemically and physically. Sialic acids commonly serve as glycosyl donors, particularly pseudaminic (Pse) or legionaminic acid (Leg) that prominently decorate eubacterial archaeal layers appendages. We investigated a new class FlmG protein glycosyltransferases modify flagellin, the structural subunit flagellar filament. Functional insulation orthologous Pse Leg biosynthesis pathways accounted for flagellin glycosylation...
Capping proteins facilitate unidirectional growth of filamentous protein assemblies formed intracellularly or extracellularly. The molecular determinants and structural transitions imposed by capping during polarized filament remain enigmatic. We show that can be uncoupled from function in a multi-subunit linear polymer: the flagellar confers motility to α-proteobacterium Caulobacter crescentus. Altering conserved region flagellin allows capping-independent assembly for multiple paralogs....