Biology subjects

Gregoire, M.

Publications and source records attributed to Gregoire, M..

7 recordsLinked to original sources

bioRxiv2026

MreB is dispensable for viability but critical for rod shape, motility and biofilm fitness in Pseudomonas aeruginosa

Despite growing interest in the MreBCD morphogenetic complex as a potential antimicrobial target, its function in Pseudomonas aeruginosa remains poorly understood. While previous studies using the MreB inhibitor A22 have established its role in cell shape maintenance and pilus regulation, the impact of mreB deletion has not been comprehensively investigated. Using genetic and microscopy-based approaches, we show that deletion of mreB is viable in P. aeruginosa, but results in spherical cells that lose all forms of motility despite retaining flagella. Importantly, we uncover a previously overlooked polar effect of the in-frame mreB deletion on the downstream mreCD genes and show, using CRISPRi-mediated silencing, that mreCD expression is essential for viability.{Delta} mreB mutants also display increased sensitivity to {beta}-lactam antibiotics and enhanced initial surface attachment, yet form more compact biofilms with reduced dispersal. In mixed-culture biofilms, spherical{Delta} mreB cells are outcompeted by rod-shaped wild-type cells and remain confined to the biofilm base. The identification of natural P. aeruginosa isolates carrying truncated mreB alleles further indicates that loss of MreB function can be tolerated in natural populations. Together, our findings reveal important contributions of the MreBCD system to viability, morphogenesis, motility and biofilm development in P. aeruginosa, providing new insights into bacterial adaptation and informing the development of targeted antimicrobial strategies.

microbiology↗

bioRxiv2026

Comparative cross-species transcriptomic analysis identifies new candidates of Pooideae nitrate response

Nitrogen fertilizers are essential for crop productivity but cause environmental harm, necessitating the development of cultivars that thrive under limited nitrogen. This study investigates the transcriptomic response to nitrate in Arabidopsis thaliana (a model dicot), Brachypodium distachyon (a model Pooideae), and Hordeum vulgare (barley, a domesticated Pooideae) to identify conserved and species-specific molecular mechanisms. Using RNA-seq after 1.5 and 3 hours of nitrate treatment, we found that core nitrate-responsive biological processes - such as nitrate transport, assimilation, carbon metabolism, and hormone signaling - are largely conserved across species. However, comparative analysis at gene level based on orthology revealed specificities between the species. For instance, rRNA processing was uniquely stimulated in Arabidopsis, while cysteine biosynthesis from serine and gibberellin biosynthesis were specifically regulated in Brachypodium and barley. Orthologs of key nitrate-responsive genes (e.g., NRT, NLP, TCP20) exhibited variable regulation, reflecting potential adaptations linked to domestication or nutrient acquisition strategies. These findings highlight the importance of integrating model and crop species to uncover targets for improving nitrogen use efficiency in cereals. This study provides a general pipeline combining Gene Ontology enrichment and orthology analysis to compare transcriptomic responses across species. This workflow is highly useful for any comparative transcriptomic study in which differences in annotation quality and gene divergence between genomes may bias interpretation.

plant biology↗

bioRxiv2025

A modified oncolytic measles virus exhibits strong immunotherapeutic potential through RIG-I activation by defective viral genomes

Oncolytic viruses can destroy tumors directly or by activating antitumor immunity, but balancing safety with potent immune stimulation remains challenging. Here, we show that deletion of the measles virus C protein, a key viral antagonist of innate immunity, reprograms the live-attenuated vaccine strain into a RIG-I-driven cancer immunotherapy. The resulting virus, MVdeltaC, accumulates defective viral genomes that activate RIG-I/MAVS signaling and trigger robust type I interferon and pro-inflammatory cytokine responses. MVdeltaC kills tumor cells more rapidly and efficiently than the parental virus and induces hallmarks of immunogenic cell death, including HMGB1 release and dendritic cell maturation. Intratumoral administration in immunocompetent mice bearing syngeneic neuroblastoma induced complete tumor regression in 90% of animals and established long-term antitumor memory. Antitumor responses were dependent on CD8 T and NK cells and were further enhanced by anti-CTLA-4 therapy or CD4 T-cell depletion. Prior measles immunization accelerated tumor clearance, indicating vaccine-boosted responses. MVdeltaC also controlled the growth of human mesothelioma, melanoma, and triple-negative breast cancer xenografts and patient-derived tumors in immunodeficient models. These findings establish MVdeltaC as a clinically ready, broad-spectrum immunotherapeutic that links RIG-I activation through defective viral genome generation to elicit potent and durable antitumor immunity. IMPACT StatementA modified measles virus lacking a viral innate immunity antagonist triggers potent antitumor responses via RIG-I sensing of defective viral genomes, revealing a new strategy for cancer immunotherapy.

immunology↗

bioRxiv2023

BdNRT2A and BdNRT3.2 are the major components of the High-Affinity nitrate Transport System in Brachypodium distachyon

O_LIAn efficient nitrate uptake system contributes to the improvement of crop nitrogen use efficiency under low nitrogen availability. The High Affinity nitrate Transport System (HATS) in plants is active in low external nitrate and is mediated by a two-component system [high affinity transporters NRT2 associated to a partner protein NRT3 (NAR2)]. C_LIO_LIIn Brachypodium, the model plant for C3 cereals, we investigated the role of BdNRT2A and BdNRT3.2 through various experimental approaches including gene expression profiling, functional characterisation in heterologous system, intracellular localization by imaging, and reverse genetics via gene silencing. C_LIO_LIExpression of BdNRT2.A and BdNRT3.2 genes in response to nitrate availability fits with the characteristics of the HATS components. Co-expression of BdNRT2A and BdNRT3.2 is required for an effective nitrate transport in the heterologous expression system Xenopus oocytes. Functional interaction between BdNRT2A-GFP and BdNRT3.2-RFP fusion proteins has been observed at the plasma membrane in Arabidopsis protoplasts in transient expression experiments. BdNRT3.2 appeared to be necessary for the plasma membrane localization of BdNRT2A. 15Nitrate influx measurements with bdnrt2a mutants (two amiRNA mutants and one NaN3 induced mutant with a truncated NRT2A protein), confirmed that BdNRT2A is a major contributor of the HATS in Brachypodium. C_LIO_LIDirected mutagenesis in BdNRT2A of a conserved Ser residue (S461) specific to monocotyledons has been performed to mimic a non-phosphorylated S461A or a constitutively phosphorylated S461D, in order to evaluate its potential role in the BdNRT2A and BdNRT3.2 interaction leading to plasma membrane targeting. Interestingly, the phosphorylation status of S461 did not modify the interaction, suggesting on a more complex mechanism. C_LIO_LIIn conclusion, our data show that BdNRT2A and BdNRT3.2 are the main components of the nitrate HATS activity in Brachypodium (Bd21-3) and allow an optimal growth in low N conditions. C_LI

plant biology↗

bioRxiv2023

Spatially localized expression of glutamate decarboxylase gadB in Escherichia coli O157:H7 microcolonies in hydrogel matrix

Functional diversity within isogenic spatially organized bacterial populations has been shown to trigger emergent community properties such as stress tolerance. Taking advantage of confocal laser scanning microscopy combined with a transcriptional fluorescent fusion reporting at single cell scale the expression of the glutamic acid decarboxylase gadB in E. coli O157:H7, it was possible to visualize for the first-time spatial patterns of bacterial gene expression in microcolonies grown in a gelled matrix. The gadB gene is involved in E. coli tolerance to acidic conditions and its strong over-expression was observed locally on the periphery of embedded microcolonies grown in acidic hydrogels. This spatialization of gadB expression did not correlate with live/dead populations that appeared randomly distributed in the colonies. While the planktonic population of the pathogens was eradicated by an exposition to a pH of 2 (HCl) for 4h, mimicking a stomachal acidic stress, bacteria grown in gel-microcolonies were poorly affected by this treatment, in particular in conditions where gadB was spatially overexpressed. Consequences of these results for food safety are further discussed.

microbiology↗

bioRxiv2020

KRAS signalling in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to the development of pleural effusion and death. MPM harbours loss-of-function mutations in genes like BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here we show that a significant proportion of human MPM harbour point mutations and copy number alterations in the KRAS proto-oncogene. These mutations are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes MPM. Murine MPM cell lines derived from these tumours carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS mutations likely play an important and underestimated role in MPM, which warrants further exploration.

physiology↗

bioRxiv2020

Mass cytometry and artificial intelligence define CD169 as a specific marker of SARS-CoV2-induced acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is the main complication of COVID-19, requiring admission to Intensive Care Unit (ICU). Despite recent immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS specifically differs from other causes of ARDS remains unknown, To address this question, we built 3 cohorts of patients categorized in COVID-19negARDSpos, COVID-19posARDSpos, and COVID-19posARDSneg, and compared their immune landscape analyzed by high-dimensional mass cytometry on peripheral blood followed by artificial intelligence analysis. A cell signature associating S100A9/calprotectin-producing CD169pos monocytes, plasmablasts, and Th1 cells was specifically found in COVID-19posARDSpos, unlike COVID-19negARDSpos patients. Moreover, this signature was shared by COVID-19posARDSneg patients, suggesting severe COVID-19 patients, whatever they experienced or not ARDS, displayed similar immune dysfunctions. We also showed an increase in CD14posHLA-DRlow and CD14lowCD16pos monocytes correlated to the occurrence of adverse events during ICU stay. Our study demonstrates that COVID-19-associated ARDS display a specific immune profile, and might benefit from personalized therapy in addition to standard ARDS management. One Sentence SummaryCOVID-19-associated ARDS is biologically distinct from other causes of ARDS.

immunology↗