Biology subjects

Robert, L.

Publications and source records attributed to Robert, L..

6 recordsLinked to original sources

bioRxiv2026

Ecology, genomics and biocontrol potential of bacteriophages infecting the bacterial wilt pathogen Ralstonia solanacearum species complex in Reunion Island

The Ralstonia solanacearum species complex (RSSC), the causal agent of bacterial wilt, is among the most destructive soil-borne plant pathogens worldwide, yet effective and sustainable control strategies remain limited. Bacteriophages represent promising biocontrol agents, but their efficacy depends on ecological compatibility with local pathogen populations. Here, we combined ecological sampling, comparative genomics, phenotypic characterization and plant assays to investigate RSSC-infecting phages in Reunion Island and evaluate their biocontrol potential. We isolated 45 phages from diverse agricultural matrices and obtained complete genome sequences for 35 novel isolates. Phylogenomic analyses revealed a locally diversified assemblage comprising multiple known taxa and several putative new genera, forming clusters largely distinct from global reference phages. Phage diversity and antibacterial activity were structured primarily by bacterial phylogeny rather than plant host or geographic origin, indicating that plants act mainly as ecological interfaces while environmental bacterial populations shape phage specialization. The community displayed two contrasting evolutionary strategies: expanding virulent lineages associated with strong antibacterial activity and persistent temperate lineages carrying integration and host-interaction functions. Host-range assays confirmed phylotype-dependent susceptibility, and strictly lytic phages showed consistently higher inhibitory activity. Guided by combined genomic and phenotypic screening, we designed a multi-family phage cocktail targeting dominant local RSSC lineages. The cocktail exhibited strong in vitro suppression of bacterial growth and significantly reduced disease severity in tomato plants. Together, our results demonstrate that effective phage biocontrol depends on evolutionary matching between phages and regional pathogen populations. Integrating ecological, genomic and functional characterization provides a robust framework for selecting locally adapted phages and developing durable phage-based strategies for managing bacterial wilt.

microbiology↗

bioRxiv2024

Regenerative potential of human enteric glia in a preclinical model of acute brain injury

BackgroundAcute brain injury is characterized by extensive tissue damage, resulting in neuronal loss and functional deficits in patients. The capacity of nerve tissue to self-regenerate is insufficient to repair damaged tissue, thus therapies based on exogenous cells are urgently needed. Human enteric glia (EG) have interesting intrinsic properties that make them a valuable candidate for regenerative medicine. In this long-term study, we investigated whether human EG treatment induces tissue repair and improves functional recovery in a rat model of brain injury. MethodsAcute brain injury was induced by malonate injection in the motor cortex of female rats, causing extensive tissue damage and long-lasting sensorimotor deficits. Human EG were isolated from gut tissue, expanded and administered intranasally in awake immunocompetent rats. To determine the long-term safety and efficacy of human EG treatment, longitudinal evaluation of sensorimotor function, post-mortem tissue regeneration and the fate of human EG were assessed thirty-six weeks after intranasal administration. ResultsTransplanted human EG satisfied the safety criteria, non-immunogenic and non-tumorigenic, required for cell therapy; they were well tolerated in immunocompetent rats, and induced sensorimotor improvement. Importantly, thirty-six weeks post-treatment, intranasally delivered human EG were detected in the rat brain, mainly in the injured motor cortex. This indicated that transplanted human EG migrated and successfully engrafted and integrated with the host tissue. Additionally, human EG induced tissue regeneration by enhancing endogenous angiogenesis and neurogenesis. Notably, thirty-six weeks after administration, human EG generated mature neurons that were enveloped by oligodendrocytes and formed synaptic connections with the host tissue. ConclusionsTransplanted human EG induced tissue repair and showed regenerative potential after brain injury. This is the first study demonstrating the feasibility, safety and efficacy of intranasal administration of human EG for treatment of brain injury.

neuroscience↗

bioRxiv2023

A genome catalog of the early-life human skin microbiome

Metagenome-assembled genomes have greatly expanded the reference genomes for skin microbiome. However, the current reference genomes are largely based on samples from adults in North America and lack representation from infants and individuals from other continents. Here we used ultra-deep shotgun metagenomic sequencing to profile the skin microbiota of 215 infants at age 2-3 months and 12 months who were part of the VITALITY trial in Australia as well as 67 maternally-matched samples. Based on the infant samples, we present the Early-Life Skin Genomes (ELSG) catalog, comprising 9,194 bacterial genomes from 1,029 species, 206 fungal genomes from 13 species, and 39 eukaryotic viral sequences. This genome catalog substantially expands the diversity of species previously known to comprise human skin microbiome and improves the classification rate of sequenced data by 25%. The protein catalog derived from these genomes provides insights into the functional elements such as defense mechanisms that distinguish early-life skin microbiome. We also found evidence for vertical transmission at the microbial community, individual skin bacterial species and strain levels between mothers and infants. Overall, the ELSG catalog uncovers the skin microbiome of a previously underrepresented age group and population and provides a comprehensive view of human skin microbiome diversity, function, and transmission in early life.

genomics↗

bioRxiv2019

Trajectories from Snapshots: Integrated proteomic and metabolic single-cell assays reveal multiple independent adaptive responses to drug tolerance in a BRAF-mutant melanoma cell line

The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge, with relevance towards understanding biological changes ranging from cellular differentiation to epigenetic (adaptive) responses of diseased cells to drugging. We report on a combined experimental and theoretic method for determining the trajectories that specific highly plastic BRAFV600E mutant patient-derived melanoma cancer cells take between drug-naive and drug-tolerant states. Recent studies have implicated non-genetic, fast-acting resistance mechanisms are activated in these cells following BRAF inhibition. While single-cell highly multiplex omics tools can yield snapshots of the cell state space landscape sampled at any given time point, individual cell trajectories must be inferred from a kinetic series of snapshots, and that inference can be confounded by stochastic cell state switching. Using a microfludic-based single-cell integrated proteomic and metabolic assay, we assayed for a panel of signaling, phenotypic, and metabolic regulators at four time points during the first five days of drug treatment. Dimensional reduction of the resultant data set, coupled with information theoretic analysis, uncovered a complex cell state landscape and identified two distinct paths connecting drug-naive and drug-tolerant states. Cells are shown to exclusively traverse one of the two pathways depending on the level of the lineage restricted transcription factor MITF in the drug-naive cells. The two trajectories are associated with distinct signaling and metabolic susceptibilities, and are independently druggable. Our results update the paradigm of adaptive resistance development in an isogenic cell population and offer insight into the design of more effective combination therapies.

bioengineering↗

bioRxiv2019

Kinetic Inference Resolves Epigenetic Mechanism of Drug Resistance in Melanoma

Drug-induced dedifferentiation towards a drug-tolerant persister state is a common mechanism cancer cells exploit to escape therapies, posing a significant obstacle to sustained therapeutic efficacy. The dynamic coordination of epigenomic and transcriptomic programs at the early-stage of drug exposure, which initiates and orchestrates these reversible dedifferentiation events, remains largely unexplored. Here we employ high-temporal-resolution multi-omics profiling, information-theoretic approaches, and dynamic system modeling to probe these processes in BRAF-mutant melanoma models and patient specimens. We uncover a hysteretic transition trajectory of melanoma cells in response to oncogene inhibition and subsequent release, driven by the sequential operation of two tightly coupled transcriptional waves, which orchestrate genome-scale chromatin state reconfiguration. Modeling of the transcriptional wave interactions predicts NF-{kappa}B/RelA-driven chromatin remodeling as the underlying mechanism of cell-state dedifferentiation, a finding we validate experimentally. Our results identify critical RelA-target genes that are epigenetically modulated to drive this process, establishing a quantitative epigenome gauge to measure cell-state plasticity in melanomas, which supports the potential use of drugs targeting epigenetic machineries to potentiate oncogene inhibition. Extending our investigation to other cancer models, we identify oxidative stress-mediated NF-{kappa}B/RelA activation as a common mechanism driving cellular transitions towards drug-tolerant persister states, revealing a novel and pivotal role for the NF-{kappa}B signaling axis in linking cellular oxidative stress to cancer progression.

cancer biology↗

bioRxiv2019

HA Nanocarriers Mediate HepG2 Vaccine Induction of hGM-CSF Gene Antitumor effect study

This report developed a novel method to observe the anti-tumor effect of HA nanoparticle carrier-mediated HepG2 cell vaccine transfected with hGM-CSF gene in vitro, and provide evidence for the clinical application of hGM-CSF gene-modified HepG2 cell vaccine. HA nanoparticle-mediated hGM-CSF gene transfection of HepG2 cells was used to prepare HepG2 cell vaccine transfected with GMCSF gene. Human PBMC were isolated by density gradient centrifugation and human PBMC were induced in vitro. The proliferative activity of PBMC and the killing effect on HepG2 cells were determined by WST-1 method. The positive expression rates of CD4+ and CD8+ were analyzed by flow cytometry, and the secretion of INF-{gamma} was determined by ELISA. WST-1 results showed that the transgenic HepG2 vaccine induced PBMC proliferation, and its proliferation rate was better than that of wild-type vaccine. The induced PBMC had a higher killing rate against HepG2 than the wild-type vaccine group and each blank. In the control group, FCM results showed that the positive expression rates of CD4+ and CD8+ in the transgenic HepG2 vaccine group were higher than those in the wild-type vaccine group and each blank control group. The ELISA results showed that the IFN-{gamma} content in the transgenic PBMC culture supernatant was 1989.76. +/- 254.21 pg/ml, higher than the wild-type vaccine group and each blank control group.

bioengineering↗