A5075349013- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Peptidase Inhibition and Analysis
- Antimicrobial Resistance in Staphylococcus
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Click Chemistry and Applications
- Antibiotic Resistance in Bacteria
- Computational Drug Discovery Methods
- Lymphoma Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Analysis
- Medical Imaging Techniques and Applications
- Probiotics and Fermented Foods
- Microbial Natural Products and Biosynthesis
- Protein Structure and Dynamics
- Microbial Metabolism and Applications
- Enzyme Production and Characterization
- Glioma Diagnosis and Treatment
- Biochemical and Molecular Research
- Lung Cancer Treatments and Mutations
- Reproductive tract infections research
- CNS Lymphoma Diagnosis and Treatment
- Bacterial biofilms and quorum sensing
Institut de Biologie Intégrative de la Cellule
2015-2022
Centre National de la Recherche Scientifique
2012-2021
CEA Paris-Saclay
2016-2021
Université Paris-Saclay
2016-2021
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2013-2021
Université de Caen Normandie
2013-2019
Normandie Université
2019
Université Paris-Sud
2008-2018
Cyceron
2013-2015
Institut de Biochimie et Biophysique Moléculaire et Cellulaire
2008-2014
We have designed, synthesized, and evaluated 5-benzylidenerhodanine- 5-benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial enzyme MurD with E. coli IC50 in the range 45−206 μM. The high-resolution crystal structure complex (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5-ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid [(R)-32] revealed details binding mode inhibitor within active site provides a good foundation for structure-based design novel generation inhibitors.
c-di-AMP is an important second messenger molecule that plays a pivotal role in regulating fundamental cellular processes, including osmotic and cell wall homeostasis many Gram-positive organisms. In the opportunistic human pathogen Staphylococcus aureus, produced by membrane-anchored DacA enzyme. Inactivation of this enzyme leads to growth arrest under standard laboratory conditions re-sensitization methicillin-resistant S. aureus (MRSA) strains ß-lactam antibiotics. The gene coding for...
Abstract The non‐toxic B‐subunit of Shiga toxin (STxB) interacts with the glycolipid Gb 3 , which is preferentially expressed on dendritic cells (DC) and B cells. After administration STxB chemically coupled to OVA (STxB‐OVA) in mice, we showed that immunodominant 257–264 peptide restricted by K b molecules specifically presented CD11c + CD8α – DC, some them displaying a mature phenotype. Using mice carrying transgene encoding diphtheria receptor (DTR) under control murine promoter, allows...
The bacterial cell wall peptidoglycan contains unusual l- and d-amino acids assembled as branched peptides. Insight into the biosynthesis of polymer has been hampered by limited access to substrates suitable polymerization assays. Here we report full synthesis peptide stem precursors from two pathogenic bacteria, Enterococcus faecium Mycobacterium tuberculosis, development a sensitive post-derivatization assay for their cross-linking l,d-transpeptidases. Access series peptides showed that...
The Mur ligases play an essential role in the biosynthesis of bacterial cell-wall peptidoglycan and thus represent attractive targets for design novel antibacterials. These enzymes catalyze stepwise formation peptide moiety disaccharide monomer unit. MurC is responsible addition first residue (l-alanine) onto nucleotide precursor UDP-MurNAc. Phosphorylation proteins by Ser/Thr protein kinases has recently emerged as a major physiological mechanism regulation prokaryotes. Herein, hypothesis...
MurD and MurE ligases, consecutive enzymes participating in the intracellular steps of bacterial peptidoglycan biosynthesis, are important targets for antibacterial drug discovery. We have designed, synthesized, evaluated first d-glutamic acid-containing dual inhibitor ligases from Escherichia coli Staphylococcus aureus (IC50 values between 6.4 180 μM) possessing activity against Gram-positive S. its methicillin-resistant strain (MRSA) with minimal inhibitory concentration (MIC) 8 μg/mL. The...
vanGCd, a cryptic gene cluster highly homologous to the vanG of Enterococcus faecalis is largely spread in Clostridium difficile. Since emergence vancomycin resistance would have dramatic clinical consequences, we evaluated capacity vanGCd confer resistance. We showed that expression inducible by and VanGCd , VanXYCd VanTCd are functional, exhibiting D-Ala : D-Ser ligase, D,D-dipeptidase racemase activities respectively. In other bacteria, these enzymes sufficient promote...
Colicin M (ColM) is the only enzymatic colicin reported to date that inhibits cell wall peptidoglycan biosynthesis. It catalyzes specific degradation of lipid intermediates involved in this pathway, thereby provoking lysis susceptible Escherichia coli cells. A gene encoding a homologue ColM was detected within exoU-containing genomic island carried by certain pathogenic Pseudomonas aeruginosa strains. This bacteriocin (pyocin) we have named PaeM crystallized, and its structure with without...
A gene named ltsA was earlier identified in Rhodococcus and Corynebacterium species while screening for mutations leading to increased cell susceptibility lysozyme. The encoded protein belonged a huge family of glutamine amidotransferases whose members catalyze amide nitrogen transfer from various specific acceptor substrates. We here describe detailed physiological biochemical investigations demonstrating the role LtsA glutamicum (LtsACg) modification by amidation wall peptidoglycan...
To gain insight into the catalytic mechanism of non-ribosomal amino acid transferases, peptidyl-RNA conjugates were synthesized for co-crystallization with FemXWv Weissella viridescens, which transfers L-Ala from Ala-tRNAAla to peptidoglycan precursor UDP-MurNAc-pentapeptide. The structure resulting complex and mutational studies revealed by binds its substrates substrate-assisted catalysis stabilization tetrahedral intermediate. As a service our authors readers, this journal provides...
Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects activity catalytic domain, three putative hydrolases were biochemically structurally characterized. These enzymes all have γ-d-Glu-A2pm (A2pm is diaminopimelic acid) cysteine amidase (or dl-endopeptidase) activities but different substrate specificities. One enzyme a lysin that cleaves peptidoglycan (PG), while other two...
Bypass of the penicillin-binding proteins by an L,D-transpeptidase (Ldt(fm)) confers cross-resistance to beta-lactam and glycopeptide antibiotics in mutants Enterococcus faecium selected vitro. Ldt(fm) is produced parental strain D344S although it insignificantly contributes peptidoglycan cross-linking as pentapeptide stems cannot be used acyl donors this enzyme. Here we show that production tetrapeptide substrate controlled a two-component regulatory system (DdcRS)...
Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by visible light the appropriate wavelength. Several approaches to increasing specificity photosensitizers for cancerous tissues and, in particular, through their conjugation ligands that are directed against tumor-associated antigens have been investigated. Here, we studied delivery photocytotoxic porphyrin compound TPP(p-O-beta-D-GluOH)3 into tumor cells overexpress glycosphingolipid Gb3,...
ABSTRACT Chlamydiae are unusual obligately intracellular bacteria that do not synthesize detectable peptidoglycan. However, they possess genes appear to encode products with peptidoglycan biosynthetic activity. Bioinformatic analysis predicts chlamydial MurE possesses UDP-MurNAc- l -Ala- d -Glu: meso -diaminopimelic acid (UDP-MurNAc- -A 2 pm) ligase Nevertheless, there no experimental data confirm this hypothesis. In paper we demonstrate the murE gene from Chlamydia trachomatis is capable of...
Abstract Peptidyl–RNA conjugates have various applications in studying the ribosome and enzymes participating tRNA‐dependent pathways such as Fem transferases peptidoglycan synthesis. Herein a convergent synthesis of peptidyl–RNAs based on Huisgen–Sharpless cycloaddition for final ligation step is developed. Azides alkynes are introduced into tRNA UDP‐MurNAc‐pentapeptide, respectively. Synthesis 2′‐azido RNA helix starts from 2′‐azido‐2′‐deoxyadenosine that coupled to deoxycytidine by...
Peptidoglycan is a major component of the bacterial cell wall and thus determinant shape. Its biosynthesis initiated by several sequential reactions catalyzed cytoplasmic Mur enzymes. ligases (MurC, -D, -E, -F) are essential for bacteria, metabolize molecules not present in eukaryotes, structurally biochemically tractable. However, although many inhibitors have been developed, few shown promising antibacterial activity, prompting hypothesis that within cytoplasm, enzymes could exist as...