Biology subjects

Clement, E.

Publications and source records attributed to Clement, E..

9 recordsLinked to original sources

bioRxiv2026

The chemorepellent effect of metformin limits bacterial penetration into mammalian mucus by altering bacterial motility

Metformin improves metabolic health and remodels the intestinal microbiota, yet how these microbial changes contribute to therapeutic benefits remains incompletely understood. We combined human metagenomics, quantitative analyses of bacterial behavior and ex vivo mucus models to investigate how metformin modulates host-microbiota interactions. Human metagenomics revealed metformin-associated enrichment of chemotaxis- and motility-related genes. At millimolar concentrations, metformin acted as a bacterial chemorepellent, an effect abolished by deletion of the chemotaxis regulator CheY and dependent on the chemoreceptor Tsr. Direct metformin exposure or fecal water from metformin-treated individuals reduced bacterial penetration into mucin, an effect reproduced in intestinal mucus from pigs fed a moderate-fat diet. Metformin treatment was further associated with reduced fecal flagellin activity and increased anti-flagellin IgA. Together, these findings identify bacterial chemotaxis as a target of metformin and reveal a mechanism by which metformin may limit bacterial access to the intestinal mucus barrier.

microbiology↗

bioRxiv2026

How motile bacteria move water in soil

Although rhizosphere microbiomes are known to enhance plants resistance to water stress, it is believed that only fungi actively contribute to the transport and uptake of water. We investigated the biomechanical impact of bacterial motility on water transport in soil by combining surface tension measurements and water infiltration experiments in soil microcosms. We observed that flagellar-based motility in the of the rhizobacteria Bacillus subtilis cells reduces the apparent surface tension of fluids by up to 15%. The effect reported depends on cell density and swimming speed, confirming its biomechanical origin, and was able to accelerate water infiltration and rewetting of soil. We conclude that Bacillus subtilis facilitates soil water transport through the deformation of air water interfaces in pores. SignificanceWater and light limitations to photosynthesis rarely occur simultaneously enabling plants in arid environments to allocate a greater proportion of assimilated carbon to belowground growth, particularly to rhizodeposition. Using microbial activity to convert chemical energy into mechanical work within soil pores offers a major opportunity for improving water use efficiency in agriculture, especially as farming shifts from polluting, energy-intensive mineral fertilisers toward resilient biological fertilisation alternatives.

biophysics↗

bioRxiv2025

Loss of CTLH component MAEA impairs DNA repair and replication and leads to developmental delay

Ubiquitin E3 ligases play crucial roles in the DNA damage response (DDR) by modulating the turnover, localization, activation, and interactions of DDR and DNA replication proteins. To gain further insight into how the ubiquitin system regulates the DDR, we performed a CRISPR-Cas9 knockout screen focused on E3 ligases and related proteins with the DNA topoisomerase I inhibitor, camptothecin. This uncovered the CTLH ubiquitin E3 ligase complex -- and particularly one of its core subunits, MAEA -- as a critical regulator of the cellular response to single-ended DNA double-strand breaks (seDSBs) and replication stress. In tandem, we identified patients with variants in MAEA who present with neurodevelopmental deficits including global developmental delay, dysmorphic facial features, brain abnormalities, intellectual disability, and abnormal movement. Analysis of patient-derived cell lines and mutation modeling reveal an underlying defect in HR-dependent DNA repair and replication fork restart as a likely cause of disease. We propose that MAEA dysfunction hinders DNA repair by reducing the efficiency of RAD51 loading at sites of DNA damage, which compromises genome integrity and cell division during development.

genetics↗

bioRxiv2025

Disruption of IgA-mediated aggregation at weaning favors mucus encroachment by commensal bacteria

Disruption of the gut mucus barrier is a critical step in the development of infec-tious or chronic inflammatory diseases. However, there are no clear links between developmental stages, diet, and the mechanical and biochemical properties of mucus. The transition from suckling to weaning is a pivotal stage in the devel-opment of the mucus barrier in mammals, with significant implications for the health and morbidity of mammalian infants. Here, using a novel microfluidic device, we investigate the penetration and organizational properties of motile Escherichia coli bacteria at the mucus interface using purified intestinal mucus collected from cohorts of piglets before and after weaning. In weaned piglets, E. coli penetrate more than 100 {micro}m into the mucus, a distance greater than the physiological thickness of the mucus layer in vivo. In contrast, for suckling piglets significant bacterial aggregation is observed at the interface, hindering the pene-tration process. Using the supernatant obtained from purified mucus of suckling piglets, we were able to restore bacterial aggregation in weaned piglet mucus and limit penetration. Interestingly, we also achieved the same result using purified human breast milk immunoglobulin A (IgA), which is known to promote bacterial aggregation. Our results emphasize the importance of mucosal immunoglobulin A (IgA) specificity in relation to the mothers immunological history, which is primarily transmitted through breast milk and lost during weaning. This also might explain why the suckling/weaning transition is, among other issues, a crit-ical window associated with a high incidence of gastrointestinal infections, before autologous IgA-mediated definite protection is acquired. Studying bacterial pen-etration in complex fluids using this new in vitro microfluidic device will pave the way for future research and the development of predictive tools for use in medical research trials.

microbiology↗

bioRxiv2025

Medium-assisted tumbling controls bacteria exploration in a complex fluid

In nature, many fluids that harbor bacterial populations or protect against microbial contamination exhibit non-Newtonian rheology. To study the spatial exploration of E.coli bacteria, a model multi-flagellated microorganism, in such complex environments, we design a motility medium with tunable macroscopic rheology. By increasing the solid charge in soft carbomer grains, we transition from a Newtonian viscous suspension to a yield-stress fluid. Using a 3D Lagrangian tracking device, we collect many individual bacterial tracks and characterize changes in motility properties such as swimming speed, persistence times and diffusivity for both a wild-type and a smooth runner mutant, up to the formation of a motility barrier at higher carbomer concentrations. We show that the presence of local mechanical disorder and resistance to penetration essentially override the biologically driven run-and-tumble navigation process. This "medium-assisted" exploration scenario is characterized by directional switching and stop-and-go kinematics and is closely related to the flexibility of the flagellar bundle.

biophysics↗

bioRxiv2025

Run-and-tumble dynamics of E. coli is governed by its mechanical properties

The huge variety of microorganisms motivates fundamental studies of their behavior with a possibility to construct artificial mimics. A prominent example is the E. coli bacterium which employs several helical flagella to exhibit a motility pattern that alternates between run (directional swimming) and tumble (change in swimming direction) phases. We establish a detailed E. coli model, coupled to fluid flow described by the dissipative particle dynamics method, and investigate its run-and-tumble behavior. Different E. coli characteristics, including body geometry, flagella bending rigidity, the number of flagella and their arrangement at the body are considered. Experiments are also performed to directly compare with the model. Interestingly, in both simulations and experiments, the swimming velocity is nearly independent of the number of flagella. The rigidity of a hook (the short part of a flagellum which connects it directly to the motor), polymorphic transformation (spontaneous change in flagella helicity) of flagella, and their arrangement at the body surface strongly influence the run-and-tumble behavior. Mesoscale hydrodynamics simulations with the developed model help us better understand physical mechanisms which govern E. coli dynamics, yielding the run-and-tumble behavior that compares well with experimental observations. This model can further be used to explore the behavior of E. coli and other peritrichous bacteria in more complex realistic environments.

biophysics↗

bioRxiv2019

Adipocyte vesicles: ‘all-in-one’ packages that stimulate tumor mitochondrial metabolism and dynamics

Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes promote melanoma aggressiveness through fatty acid oxidation, with a heightened effect in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation after release through lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance in obesity.

cancer biology↗

bioRxiv2018

Contribution of Retrotransposition to Developmental Disorders

Mobile genetic Elements (MEs) are segments of DNA which, through an RNA intermediate, can generate new copies of themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. As such, we have identified RT-derived events in 9,738 exome sequenced trios with DD-affected probands as part of the Deciphering Developmental Disorders (DDD) study. We have ascertained 9 de novo MEs, 4 of which are likely causative of the patients symptoms (0.04% of probands), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we have estimated genome-wide germline ME mutagenesis and constraint and demonstrated that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.

genetics↗

bioRxiv2018

Rapid Paediatric Sequencing (RaPS): Comprehensive real-life workflow for rapid diagnosis of critically ill children

BackgroundRare genetic conditions are frequent risk factors for, or direct causes of, organ failure requiring paediatric intensive care unit (PICU) support. Such conditions are frequently suspected but unidentified at PICU admission. Compassionate and effective care is greatly assisted by definitive diagnostic information. There is therefore a need to provide a rapid genetic diagnosis to inform clinical management.\n\nTo date, Whole Genome Sequencing (WGS) approaches have proved successful in diagnosing a proportion of children with rare diseases, but results may take months to report or require the use of equipment and practices not compatible with a clinical diagnostic setting. We describe an end-to-end workflow for the use of rapid WGS for diagnosis in critically ill children in a UK National Health Service (NHS) diagnostic setting.\n\nMethodsWe sought to establish a multidisciplinary Rapid Paediatric Sequencing (RaPS) team for case selection, trio WGS, a rapid bioinformatics pipeline for sequence analysis and a phased analysis and reporting system to prioritise genes with a high likelihood of being causal. Our workflow was iteratively developed prospectively during the analysis of the first 10 children and applied to the following 14 to assess its utility.\n\nFindingsTrio WGS in 24 critically ill children led to a molecular diagnosis in ten (42%) through the identification of causative genetic variants. In three of these ten individuals (30%) the diagnostic result had an immediate impact on the individuals clinical management. For the last 14 trios, the shortest time taken to reach a provisional diagnosis was four days (median 7 days).\n\nInterpretationRapid WGS can be used to diagnose and inform management of critically ill children using widely available off the shelf products within the constraints of an NHS clinical diagnostic setting. We provide a robust workflow that will inform and facilitate the rollout of rapid genome sequencing in the NHS and other healthcare systems globally.\n\nFundingThe study was funded by NIHR GOSH/UCL BRC: ormbrc-2012-1

genomics↗