Biology subjects

Rouyer, L.

Publications and source records attributed to Rouyer, L..

5 recordsLinked to original sources

bioRxiv2026

Co-translational O-glycosylation driven by GALNTs spatial reprogramming fosters pancreatic cancer growth

Signal-driven relocation of GalNAc-transferases (GALNTs) from the Golgi to the ER, termed GALA, promotes tumour growth, but its effects on glycosylation are unclear. Unlike N-glycosylation, which is co-translational, O-glycosylation initiates post-translationally in the Golgi. Here we show that GALA subverts this arrangement in pancreatic ductal adenocarcinomas (PDAC) and in murine pancreatic tumours, where it stimulates growth. Quantitative glycoproteomics on a cellular model reveals a substantial expansion of the O-glycoproteome, consisting in thousands of sites across hundreds of proteins, ER-resident proteins, cell-surface receptors, secreted factors, and extracellular matrix components. Profiling of murine tumours and patient-derived xenografts confirms widespread activation and cross-species conservation of glycosylation patterns. Structural analysis reveals that GALA-specific residues have solvent accessibility as low as N-glycosylation sites, and below Golgi O-glycosylation or phosphorylation sites, indicating that ER O-glycosylation occurs co-translationally. By inverting the normal temporal sequence of folding and glycosylation, cancer cells generate alternative glycoforms that foster tumour growth.

cancer biology↗

bioRxiv2026

Plant associated bacteria are a rich reservoir for multidrug efflux pumps

Plants produce antibiotic substances and bacteria need to cope with those substances to colonize plants. We analyzed the inventory of genes encoding resistance-nodulation-cell division (RND) efflux pumps originating from 282 bacterial isolates from leaves or roots of the model plant Arabidopsis thaliana. We confirmed that, on average, plant associated bacteria hold a significantly increased repertoire of genes encoding RND antiporters homologs compared to strains isolated from other ecological niches, as reported in a previous study. While some RND antiporter clades were enriched in plant colonizers, other clades found in the genomes of isolates from other environments were underrepresented. An in-depth analysis of RND antiporters from plant colonizing bacteria revealed that conserved motifs can be found in each clade, possibly contributing to substrate specificity. Interestingly, we found horizontal gene transfer markers in 10% of the antiporter homologs, suggesting that horizontal gene transfer may significantly contribute to the adaptation of bacteria to the specific chemical environment created by different organs of plant hosts. In addition, homologs from leaf-isolated bacteria showed a lower diversification, and harbored markers of horizontal gene transfer in the heavy metal exporting clade. Sequence and structural analysis revealed a high diversity in RND-antiporters, with few residues under purifying selection, indicating that RND diversity is driven by random mutations. Our findings have major implications for the origin of multidrug resistances and for our understanding of the forces shaping the outcome of plant-microbe ecology in general.

microbiology↗

bioRxiv2025

Plant specialised metabolites modulate the molecular signatures of host-bacteria and bacteria-bacteria interactions

Plants participate in intricate interactions with a multitude of microorganisms, many of which also influence each other. This holobiont is situated in a chemical soil environment that is defined, in parts, by the specialised metabolite legacy of proximal and preceding organisms, including other plants. Here, we investigated the influence of external plant-derived specialised metabolites on the interactions among root-associated bacterial strains, and between these strains and a plant host. Using benzoxazinoids and their derivatives as a model in both simplified pairwise experiments and more complex multi-organism analyses, we show that these chemicals can modulate bacteria-bacteria, as well as bacteria-plant interactions. While the chemical environment alone had little effect on the plant at the molecular level, it differentially affected plant chemical defences, immunity, and sugar transport when combined with single-isolate or micro-community inoculums. Our study underlines the importance of the chemical environment in modulating organismic interactions and illustrates the value of combining reduced-complexity, bottom-up reconstruction approaches with top-down holobiont profiling. SIGNIFICANCEMany plant species secrete specialized metabolites into the soil, where they can have a long-lasting effect on subsequent plant generations and their associated microbiomes. Understanding the effect of this chemical environment on soil- and plant-associated microbiomes is crucial to determine the impact of soil legacy on host plants, for example in the context of crop rotations. Here, we report that the interactions among root-associated microbes are modulated by specialized metabolites of the benzoxazinoid family, which are prominent metabolites in many grasses. We further show that the chemical environment can inhibit the defence capacity of the plant towards colonizing bacteria, and that more complex bacterial communities are able to mitigate these effects. Our work highlights the importance of deconstructing bacterial communities and the chemical environment to gain insights into the fine-tuned molecular mechanisms that determine the outcome of complex organismic interactions.

plant biology↗

bioRxiv2025

Cancer cells transfer invasive properties through microRNAs contained in collagen-tracks

Invasion is a prerequisite for metastasis formation. During tumor development, the extracellular matrix (ECM) is remodeled in part through overexpression of type I collagen, increasing tumor microenvironment stiffness, and facilitating cancer dissemination. During breast cancer cell migration, we observed membrane debris left behind, attached to the collagen fibrils, along the migration path. We named these structures collagen-tracks. These collagen-tracks can be deposited in 3D matrices in vitro and in vivo and their formation is stimulated by the interaction between the ECM and matrix receptors, such as the discoidin-domain receptor (DDR1). However, they are different from structures already known to be involved in cell-cell communication such as exosomes and migrasomes, due to their specific nucleic acid and protein contents. When deposited by highly invasive breast cancer cells, internalized collagen-tracks reprogram non-invasive cells into highly pro-metastatic ones by inducing a partial epithelial-mesenchymal transition (EMT). This cell reprogramming is dependent on specific miRNAs present in the collagen-tracks, that are necessary to promote ECM degradation, increase cell motility and invasiveness. Collagen-tracks thus represent a new form of cell-cell communication important for driving tumor invasion that could be targeted to prevent metastasis.

cell biology↗

bioRxiv2023

The lactonase BxdA mediates metabolic adaptation of maize root bacteria to benzoxazinoids

Root exudates contain secondary metabolites that affect the plants root microbiome. How microbes cope with these bioactive compounds, and how this ability shapes root microbiomes remain largely unknown. We investigated how maize root bacteria metabolise benzoxazinoids, the main specialised metabolites of maize. Diverse and abundant bacteria metabolised the major compound (6-methoxy-benzoxazolin-2-one, MBOA) in the maize rhizosphere to 2-amino-7-methoxyphenoxazin-3-one (AMPO). By contrast, bacteria isolated from Arabidopsis, which does not produce benzoxazinoids, were unable to metabolise MBOA. Among Microbacteria strains, this differential metabolisation allowed to identify a conserved gene cluster containing the lactonase bxdA. BxdA converts MBOA to AMPO in vitro and we show that this capacity provided bacteria a growth benefit under carbon-limiting conditions. Together these results reveal that maize root bacteria - through BxdA - are metabolically adapted to the benzoxazinoids of their host. We propose that metabolic adaptation to plant-specialised compounds shapes root bacterial communities across the plant kingdom.

microbiology↗