A5065982450- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- Vibrio bacteria research studies
- RNA and protein synthesis mechanisms
- Biochemical and Structural Characterization
- Enzyme Structure and Function
- Bacterial biofilms and quorum sensing
- Ion channel regulation and function
- Signaling Pathways in Disease
- Bacterial Infections and Vaccines
- Protein Structure and Dynamics
- Salmonella and Campylobacter epidemiology
- Cancer Research and Treatments
- Connective tissue disorders research
- Pneumocystis jirovecii pneumonia detection and treatment
- Clostridium difficile and Clostridium perfringens research
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Cystic Fibrosis Research Advances
- Force Microscopy Techniques and Applications
- Streptococcal Infections and Treatments
- Cellular Mechanics and Interactions
- Antimicrobial Resistance in Staphylococcus
Centre National de la Recherche Scientifique
2014-2024
Université Paris Cité
2014-2024
Sorbonne Paris Cité
2014-2024
Cibles Thérapeutiques et conception de médicaments
2023-2024
Laboratoire de Cristallographie et RMN Biologiques
2008-2019
Sorbonne Université
2018
The University of Adelaide
2017
University College London
2009-2015
Observatoire de Paris
2015
Birkbeck, University of London
2011-2014
ABSTRACT Retrospective analysis of 189 nonredundant strains Pseudomonas aeruginosa sequentially recovered from the sputum samples 46 cystic fibrosis (CF) patients over a 10-year period (1998 to 2007) revealed that 53 out (28%) were hypersusceptible β-lactam antibiotic ticarcillin (MIC ≤ 4 μg/ml) (phenotype dubbed Tic hs ). As evidenced by trans -complementation and gene inactivation experiments, mutational upregulation efflux system MexXY was responsible for various degrees resistance...
Pilicides block pili formation by binding to pilus chaperones and blocking their function in the chaperone/usher pathway E. coli. Various C-2 substituents were introduced on pilicide scaffold design synthetic method developments. Experimental evaluation showed that proper substitution of this position affected biological activity compound. Aryl resulted pilicides with significantly increased potencies as measured pili-dependent biofilm hemagglutination assays. The structural basis PapD...
Abstract The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting large variety of antimicrobial compounds. Crystal structures MexB and its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting directional drug pathway conformational interconversion (from Loose Tight binding pockets to Open gate (LTO) for exit). It remains unclear how acquires LTO form. Here performing functional cryo-EM structural...
Previously, we pointed out in
The formation of adhesive surface structures called pili or fimbriae ('bacterial hair') is an important contributor towards bacterial pathogenicity and persistence. To fight often chronic recurrent infections such as urinary tract infections, it necessary to understand the molecular mechanism nanomachines assembling pili. Here, we focus on so far best-known pilus assembly machinery: chaperone-usher pathway producing type 1 P pili, highlight most recently acquired structural knowledge. First,...
<title>Abstract</title> Recent advances in sequencing technologies have enhanced patient diagnosis; however, causal pathogenic variants remain unidentified for a significant number of patients due to limited understanding certain variants, regulatory sequences, or challenges, such as complex rearrangements. Investigating the epigenetic landscape has become essential improve diagnostic yield. Diseases caused by regulators, often associated with growth abnormalities, intellectual disability,...
The standard analytical procedure for screening the proteomic profile of a venom often relies on an appropriate combination sample extraction, electrophoresis, reversed-phase high-performance liquid chromatography, mass spectrometry, and Edman degradation. We present in this study new approach based Fourier transform spectrometry (FTMS) analysis directly crude venom. chosen is unique from Atractaspis irregularis, species never studied at molecular level previously. This snake belongs to...
Membrane proteins are essential in the exchange processes of cells. In spite great breakthrough soluble studies, membrane structures, functions and interactions still a challenge because difficulties related to their hydrophobic properties. Most experiments performed with detergent-solubilized proteins. However widely used micellar systems far from biological two-dimensions membrane. The development new biomimetic is fundamental tackle this issue. We present an original approach that...
Efflux pumps are membrane transporters that actively extrude various substrates, leading to multidrug resistance (MDR). In this study, we have designed a new test allows investigating the assembly of MexA-MexB-OprM efflux pump from Gram negative bacteria Pseudomonas aeruginosa. The method relies on streptavidin-mediated pull-down OprM proteoliposomes upon interaction with MexAB containing biotin function carried by lipids. We give clear evidence for importance MexA in promoting and...
Type IV pili (Tfp) are expressed by many Gram-negative bacteria to promote aggregation, adhesion, internalization, twitching motility, or natural transformation. Tfp of Neisseria meningitidis, the causative agent cerebrospinal meningitis, involved in colonization human nasopharynx. After invasion bloodstream, allow adhesion N. meningitidis endothelial cells, which leads opening blood-brain barrier and meningitis. To achieve firm induces a host cell response that results elongation microvilli...
Type 1 pili are representative of a class bacterial surface structures assembled by the conserved chaperone/usher pathway and used uropathogenic Escherichia coli to attach bladder cells during infection. The outer membrane assembly platform-the usher-is critical for formation pili, catalysing polymerisation pilus subunits enabling secretion nascent pilus. Despite extensive structural characterisation usher, number questions about its mechanism remain, notably oligomerisation state, how it...
PapC ushers are outer-membrane proteins enabling assembly and secretion of P pili in uropathogenic E. coli. Their translocation domain is a large β-barrel occluded by plug domain, which displaced to allow the pilus subunits across membrane. Previous studies suggested that this gating mechanism controlled β-hairpin an α-helix. To investigate role these elements allosteric signal communication, we developed method combining evolutionary molecular dynamics native mutants lacking and/or Analysis...
The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required adhesion pathogenic E. coli, which cause the development pyelonephritis. Multiple subunits form pilus, highly specific coordinated by usher. Despite wealth structural knowledge, how catalyzes subunit polymerization orchestrates correct functional order remain unclear. Here, ability soluble N-terminal (UsherN), C-terminal (UsherC2), Plug (UsherP) domains to bind different...
Among the different mechanisms used by bacteria to resist antibiotics, active efflux plays a major role. In gram-negative bacteria, is carried out tripartite pumps that form macromolecular assembly spanning both membranes of cellular wall. At outer membrane level, well-conserved Outer Membrane Factor (OMF) protein acts as an exit duct, but its sequence varies greatly among species. The OMFs share similar tri-dimensional structure includes beta-barrel pore domain stabilizes channel within...
Multidrug resistance has become a serious concern in the treatment of bacterial infections. A prominent role is ascribed to active efflux xenobiotics out bacteria by tripartite protein machinery. The mechanism drug extrusion rather well understood, thanks X-ray structures obtained for Escherichia coli TolC/AcrA/AcrB model system and related Pseudomonas aeruginosa OprM/MexA/MexB. However, many questions remain unresolved, particular stoichiometry pump assembly. On basis blue native...
One of the major families membrane proteins found in prokaryote genome corresponds to transporters. Among them, resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one most problematic mechanisms used by bacteria resist antibiotics, i.e., active efflux drugs. In Gram-negative bacteria, these inserted inner and form a tripartite assembly with an outer factor periplasmic linker order cross two membranes expulse molecules outside cell. A lot...
Tripartite multidrug RND efflux systems made of an inner membrane transporter, outer factor (OMF) and a periplasmic adaptor protein (PAP) form canal to expel drugs across Gram-negative cell wall. Structures MexA-MexB-OprM AcrA-AcrB-TolC, from Pseudomonas aeruginosa Escherichia coli, respectively, depict reduced interfacial contact between OMF PAP, making unclear the comprehension how is recruited. Here, we show that Q93R mutation MexA located in α-hairpin domain increases antibiotic...
P pili are hair-like adhesive structures that assembled on the outer membrane (OM) of uropathogenic Escherichia coli by chaperone-usher pathway. In this pathway, chaperone-subunit complexes formed in periplasm and targeted to an OM assembly platform, usher. Pilus subunits display a large groove caused missing β-strand which, complex, is provided chaperone. At usher, pilus mechanism termed "donor-strand exchange (DSE)" whereby chaperone exchanged incoming subunit's N-terminal extension (Nte)....