Biology subjects

Dupuis, G.

Publications and source records attributed to Dupuis, G..

4 recordsLinked to original sources

bioRxiv2025

Interplay between T3SS effectors, ExoY activation, and cGMP signaling in Pseudomonas aeruginosa infection

ExoY is a nucleotidyl cyclase, secreted by the Pseudomonas aeruginosa type 3 secretion system (T3SS), which generates various cyclic nucleotides within host cells, predominantly cGMP. How ExoY-catalyzed cNMPs production contributes to the infection process remains unclear. Using recombinant P. aeruginosa strains expressing ExoY variants with different substrate specificities, we identified that ExoY-derived cGMP modulates the cytotoxicity of ExoT, a co-injected T3SS exotoxin. Our results demonstrated that dephosphorylation of the host CrkII adaptor protein, a downstream effect of the ADP-ribosyltransferase activity of ExoT, is limited by ExoY-derived cGMP, therefore antagonizing ExoT-induced cell retraction. We also revealed a reciprocal interaction between T3SS effectors, showing that ExoT and ExoS, can in turn, suppress ExoY activity and its production of cGMP in certain cell types, thereby limiting their regulation by ExoY-synthesized cGMP. These findings highlight the intricate interplay between T3SS effectors and uncover a novel host cell-dependent regulation within P. aeruginosa infections.

microbiology↗

bioRxiv2022

Interaction mechanism between the HSV-1 glycoprotein B and the antimicrobial peptide Amyloid-β

Unravelling the mystery of Alzheimers Disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being discussed in the literature, for instance, both the deposition of the Amyloid-Beta peptide (A{beta}) and the intracellular neurofibrillary tangles (NFTs) could occur within the brain without any cognitive pathology. Thus, these paradoxes suggest that something more fundamental is at play in the onset of the disease and other key and related pathomechanisms have to be investigated. The present study follows our previous investigations on the infectious hypothesis, which posits that some pathogens are linked to late onset AD. Our studies also build upon the shattering finding that A{beta} is a powerful antimicrobial agent capable of inhibiting pathogens as observed in in vitro experiments. Herein, we ask what are the molecular mechanisms in play when A{beta} neutralizes infectious pathogens? To answer this question, we probed at nanoscale lengths with FRET (Forster Resonance Energy Transfer), the interaction between A{beta} peptides and glycoprotein B (responsible of virus-cell binding) within the HSV-1 virion. We concluded that there is indeed a close interaction, likely nonspecific or semi-specific, between the two types of molecules, which participate in virus neutralization.

neuroscience↗

bioRxiv2018

BIN1 genetic risk factor for Alzheimer is sufficient to induce early structural tract alterations in entorhinal cortex-dentate gyrus pathway and related hippocampal multi-scale impairments

Genetic factors are known to contribute to Late Onset Alzheimers disease (LOAD) but their contribution to pathophysiology, specially to prodomic phases accessible to therapeutic approaches are far to be understood. To translate genetic risk of Alzheimers disease (AD) into mechanistic insight, we generated transgenic mouse lines that express a [~]195 kbp human BAC that includes only BIN1, a gene associated to LOAD. This model gives a modest BIN1 overexpression, dependent of the number of BAC copies. At 6 months of age, we detected impaired entorhinal cortex (EC)-hippocampal pathways with specific impairments in EC-dentate gyrus synaptic long-term potentiation, dendritic spines of granular cells and recognition episodic memory. Structural changes were quantified using MRI. Their whole-brain functional impact were analyzed using resting state fMRI with a hypoconnectivity centered on entorhinal cortex. These early phenotype defects independent of any changes in A-beta can be instrumental in the search for new AD drug targets.

neuroscience↗

bioRxiv2018

Combining 3D single molecule localization strategies for reproducible bioimaging

We developed a 3D localization-based super-resolution technique providing a slowly varying localization precision over a 1 m range with precisions down to 15 nm. The axial localization is performed through a combination of point spread function (PSF) shaping and supercritical angle fluorescence (SAF), which yields absolute axial information. Using a dual-view scheme, the axial detection is decoupled from the lateral detection and optimized independently to provide a weakly anisotropic 3D resolution over the imaging range. This method can be readily implemented on most homemade PSF shaping setups and provides drift-free, tilt-insensitive and achromatic results. Its insensitivity to these unavoidable experimental biases is especially adapted for multicolor 3D super-resolution microscopy, as we demonstrate by imaging cell cytoskeleton, living bacteria membranes and axon periodic submembrane scaffolds. We further illustrate the interest of the technique for biological multicolor imaging over a several-m range by direct merging of multiple acquisitions at different depths.

biophysics↗