Biology subjects

Noel, A.

Publications and source records attributed to Noel, A..

10 recordsLinked to original sources

bioRxiv2026

Development of low cost, robust and reproducible biofilm static and pharmacodynamic assays

SynopsisO_ST_ABSBackgroundC_ST_ABSThe complexity of diagnosing and treating biofilm-associated infections necessitates a comprehensive strategy to mitigate the rising rates of antimicrobial resistance (AMR). Microtiter plate methods are used globally for determination of biofilm eradication concentrations (MBEC) but few have been adapted to observe pharmacodynamic observations. Here, we describe a method which allows for both static and pharmacodynamic assays of biofilm evaluation. MethodsA total of 150 clinical isolates from Southmead Hospital were assessed, representing five bacterial species (N=30 per bacterial species): Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae. MBECs were determined using a developed method using 96 well plates and glass beads. MBECs of seven different antibiotics were compared to those determined using the established Calgary biofilm device (CBD). Dynamic pharmacodynamic evaluations to produce Biofilm Time Kill curve (BTKC) based on published planktonic time kill curve (TKC) data and ISO recommendations were carried out using the glass bead model for K. pneumoniae and ciprofloxacin, S. aureus and levofloxacin and S. pneumoniae and vancomycin. Quantification of biofilm biomass was assessed at 0, 2, 4, 8 and 24 hours and compared to planktonic culture survival under comparable challenge conditions. ResultsComparing MBEC results for all bacterial strains and antibiotic challenges showed no statistical difference between the glass bead and CBD methods (P <0.05). Biofilm BTKC AUBKC were inferior to planktonic equivalents but demonstrated specific pharmacodynamic patterns of biofilm reduction efficacy. MBEC correlated with biofilm BTKC penetration in line with clinical observations for S. aureus vs vancomycin and S. pneumoniae vs levofloxacin. ConclusionsThe glass bead biofilm models provide robust, reproducible alternatives to the traditional methods of determining MBEC and bridge the gap with biofilm pharmacodynamic evaluations. These methods also provide a low-cost option to current methods as only standard laboratory equipment is required, allowing for the generation of comprehensive data sets. This ensures greater translatability to complex in vitro models and clinical scenarios.

microbiology↗

bioRxiv2026

Implementing considered elements of standardisation for Time Kill Curve experiments across multiple sites: A European collaboration perspective

SynopsisO_ST_ABSBackgroundC_ST_ABSThe main advantages of Time Kill Curves (TKCs) in antimicrobial drug development are the ability to track bacterial kill and regrowth over time and with varying drug concentrations. Whilst there are guideline documents in place, such as M26-A in CLSI, there remains scope for individual laboratory differences in practice. Here we evaluated several factors which potentially influenced data generated in TKCs. MethodsFirstly, E. coli ATCC 25922 was used to determine optimum sampling volume, culture vessel volume, CFU enumeration variance factors and static versus agitated cultures in a single laboratory. Secondly, a ring test comprising of TKCs was performed by six laboratories focusing on: standardised inoculum, static culture and two culture vessel sizes 10 mL and 200 {micro}L. Data analysis was performed to determine consistency within centres and between them. ResultsConsistently accurate inocula could be achieved by use of: larger sampling volumes between 100 {micro}L > 20 mL; larger culture vessels volumes (10 mL > 100 {micro}L) and higher inocula (10 8 > 1.5x10 5 CFU). Culture agitation during the TKC experiment resulted in reduced killing compared to static cultures. Reproducibility of TKCs was best between centres when they were performed in 10 mL culture vessels. There was more variability per site when performing TKC in 96 well trays. ConclusionsTechnical factors such as preparation of inocula, agitation, vessel size and enumeration of cultures are important variables in performing TKCs that need to be standardised in drug development programmes involving multiple laboratory centres.

microbiology↗

bioRxiv2026

Is there a need to implement standardisation into in vitro antimicrobial evaluation systems? A European collaboration perspective

SynopsisO_ST_ABSBackgroundC_ST_ABSTime kill curve (TKC) assessments are an essential step in the study of an antimicrobials pharmacodynamic characteristics. Surprisingly TKCs have not be formally standardised, therefore there remain concerns that different testing centres/methodologies may produce different results. Six centres participating in Gram-negative-Antibiotics NOW (GNA-NOW) consortium measured a series of TKCs with meropenem against E. coli to establish: Same-day (SD) vs different-day (DD) replication per centre (intra-site), and centre to centre (inter-site) correlations. MethodsMeropenem was tested against three strains of E. coli (ATCC 25922; ESBL producer C1.55; OXA-48 producer C1.62). An inoculum of 1.5x106 CFU was specified with meropenem concentrations of x0, x1 to x16 MIC; and sampling assessment of bacterial density was determined at 0-24h. Experiments were performed in triplicate, aerobically at 37{degrees}C. Centre-specific methodology was collected. Meropenem, media, bacterial strains, were shipped from one central laboratory to participating laboratories. ANOVA and Friedman tests were used to assess SD, DD and between centre replications. ResultsAssessment of the methodologies between centres revealed many differences, including bacterial inoculum, meropenem preparation, volume of TKC vessel, vessel materials, agitation vs static cultures and sampling volumes. Intra-centre SD and DD analysis for all strains were generally associated with P>0.05 suggesting consistency. Inter-centre SD and DD comparisons resulted in P<0.05, indicating variable total bacterial load measurement between centres. ConclusionsTKC methodologies varied between different centres, and while intra-centre comparison of SD and DD were generally consistent, inter-centre comparisons were not. Standardisation of TKC methodologies is required.

microbiology↗

bioRxiv2025

Aquaporin-1 sustains lymphangiogenic responses in inflammatory microenvironments

Intestinal lymphatic vessels are essential for dietary lipid absorption and immune cell trafficking. Specialized villus lymphatic capillaries, lacteals, undergo constant VEGF-C-dependent renewal to maintain their function in a hyperosmolar, inflammatory microenvironment exposed to dietary by-products. The mechanisms of lacteal adaptation remain incompletely understood. We integrated new and published single-cell RNA-sequencing data to profile murine small-intestinal lymphatic endothelial cells (LECs) and identified three distinct subsets. Lacteal LECs display a transcriptional signature resembling Ptx3 immune-interacting LECs characterized by high expression of Aqp1, encoding the aquaporin-1 water channel. LEC-specific deletion of Aqp1 reduced lacteal length, impaired lipid uptake, and limited weight gain on a high-fat diet, underscoring the importance of water homeostasis in lacteal maintenance. AQP1 also promoted VEGF-C-dependent LEC migration under osmotic stress and, uniquely, was upregulated during inflammatory remodelling in secondary lymphedema and lymphatic malformations, but not during embryonic lymphangiogenesis. These findings link lacteal regeneration to inflammatory lymphatic remodelling and highlight tissue osmolarity as a key biophysical factor in postnatal lymphangiogenesis.

pathology↗

bioRxiv2025

Food supplementation with molybdenum complexes improves honey bee health

In this study, we evaluated the impact of supplementing honey bee feed with molybdenum-based compounds. Among a dozen of dinuclear Mo(V) complexes, we first selected the most stable and non-toxic complexes, which were tested as food supplements in an extensive eight-year campaign involving more than 700 beehives across various environmental conditions in Moldova, France, Greece and USA. This unprecedented field campaign revealed that a few milligrams of compounds Na-Mo2O4-EDTA or Li-Mo2O4-EDTA provided in spring or autumn, increased queen fecundity, hygienic behavior, and honey production, while infestation rates of worker bees and brood by the mite Varroa destructor, and mortality rates in winter were dramatically reduced. Hive monitoring showed that the Mo-containing syrup can be consumed over 1.5 months and is well assimilated by larvae and workers within the hive. In particular, Mo levels increased significantly in the head of the bees. X-ray fluorescence measurements demonstrated that Na-Mo2O4-EDTA increases Mo levels in brain, neurolemma and hypopharyngeal glands. The metabolism of Mo complexes was addressed using X-Ray photoelectron spectroscopy (XPS) on bee faeces, which revealed that the complexes are oxidized into Mo(VI) species and thus suggesting that Mo complexes may function as antioxidant agents in bees. These findings offer promising solutions for the beekeeping industry, which is struggling with weakening honey bee colonies. Significance StatementHoney bees play a crucial role as pollinators. Unfortunately, colony losses have increased significantly over the past decades through the action of multiple environmental stressors. Currently, solutions are sought to strengthen bees health and resilience. This study shows that feeding bees with small amounts of trace elements like molybdenum can improve honey bee condition and increase the production of hive products. Through an unprecedented series of field and lab tests it notably demonstrates that molybdenum complexes are i) non-toxic, ii) consumed by bees over several generations, iii) assimilated particularly in the brain and hypopharyngeal glands, iv) acting as antioxidant. These results open new avenues for using trace elements to improve pollinator health.

zoology↗

bioRxiv2025

Lactuchelins: New lipopeptide siderophores from Pseudomonas lactucae inhibit Xanthomonas campestris pv. campestris 8004

Seeds harbor diverse microbial communities, including beneficial microbes that play a vital role in protecting plants from seed-borne pathogens. Despite their critical importance, the molecular mechanisms driving intermicrobial competition within the seed microbiome remain poorly understood, limiting the potential to optimize seed inoculation strategies. In this study, we evaluated the inhibitory potential of 30 seed-borne bacterial strains against the phytopathogen Xanthomonas campestris pv. campestris 8004 (Xcc8004). We identified Pseudomonas lactucae CFBP13502 as a potent inhibitor of Xcc8004, mediated by exometabolites specifically induced in the presence of Lysobacterales (formerly Xanthomonadales). Transcriptomic analysis of CFBP13502 revealed upregulation of a gene cluster involved in the biosynthesis of a lipopeptide siderophore biosynthesis. Gene deletion confirmed that this cluster is essential for the growth inhibition of Xcc8004. Furthermore, iron supplementation abolished this inhibitory effect, providing strong evidence for the role of iron chelation. Through comparative metabolomics, we elucidated the structure of a novel family of lipopeptide siderophores, which we named lactuchelins, produced by CFBP13502. Our findings provide the first molecular evidence of competitive exclusion mechanisms at the seed microbiome interface, highlighting lactuchelins as a promising avenue for the development of seed-based biocontrol strategies against seed-borne phytopathogens.

microbiology↗

bioRxiv2024

Root associated Streptomyces produce galbonolides to modulate plant immunity and promote rhizosphere colonisation

The rhizosphere, which serves as the primary interface between plant roots and the soil, constitutes an ecological niche for a huge diversity of microbial communities. Currently, there is little knowledge on the nature and the function of the different metabolites released by rhizospheric microbes to facilitate colonization of this highly competitive environment. Here, we demonstrate how the production of galbonolides, a group of polyene macrolides that inhibit plant and fungal Inositol Phosphorylceramide Synthase (IPCS), empowers the rhizospheric Streptomyces strain AgN23, to thrive in the rhizosphere by triggering the plants defence mechanisms. Metabolomic analysis of AgN23-inoculated Arabidopsis roots revealed a strong induction in the production of an indole alkaloid, camalexin, which is a major phytoalexin in Arabidopsis. By using a plant mutant compromised in camalexin synthesis, we show that camalexin production is necessary for the successful colonization of the rhizosphere by AgN23. Conversely, hindering galbonolides biosynthesis in AgN23 knock-out mutant resulted in loss of inhibition of IPCS, a deficiency in plant defence activation, notably the production of camalexin, and a strongly reduced development of the mutant bacteria in the rhizosphere. Together, our results identified galbonolides as important metabolites mediating rhizosphere colonisation by Streptomyces. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/576418v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1ec39f3org.highwire.dtl.DTLVardef@1d0a14eorg.highwire.dtl.DTLVardef@e1f61org.highwire.dtl.DTLVardef@12e487e_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO Model summarizing the mode of action of galbonolides in stimulating plant defence to support AgN23 colonization of the rhizosphere. Galbonolides secretion by Streptomyces sp. AgN23 trigger Inositol Phosphoceramide Synthase (IPCS) inhibition in Arabidopsis root cells (orange arrow). The resulting raise in Ceramide precursors of the IPCS may result in the different defence responses associated to AgN23: Hypersensitive Responses (HR), Salicylic Acid (SA) signalling, nuclear Ca2+ influx, defence gene expression and camalexin biosynthesis. This production of camalexin (blue arrow) exert a positive effect on AgN23 growth in the rhizosphere, presumably by restricting the growth of bacterial and fungal competitors sensitive to this phytoalexin. In addition, galbonolides secretion in the rhizosphere may also directly interfere with fungal competitors of AgN23. C_FIG

microbiology↗

bioRxiv2023

DeepGEEP: Data-Driven Prediction of Bacterial Biofilm Gene Expression Profiles

Predicting the gene expression profile (GEEP) of bacterial biofilms in response to spatial, temporal, and concentration profiles of stimulus molecules holds significant potential across microbiology, biotechnology, and synthetic biology domains. However, the resource and time-intensive nature of experiments within Petri dishes presents significant challenges. Data-driven methods offer a promising avenue to replace or reduce such experiments given sufficient data. Through wellcrafted data generation techniques, the data scarcity issue can be effectively addressed. In this paper, an innovative methodology is presented for generating GEEP data over a Petri dish that results from a specific chemical stimulus release profile. A twodimensional convolutional neural network (2D-CNN) architecture is subsequently introduced to leverage the synthesized dataset to predict GEEP variations across bacterial biofilms within the Petri dish. The approach, coined DeepGEEP, is applied to data generated by a particle-based simulator (PBS) to enable a flexible evaluation of its efficacy. The proposed method attains a significant level of accuracy in comparison to established benchmark models such as Linear SVM, Radial Basis Function SVM, Decision Tree, and Random Forest.

bioinformatics↗

bioRxiv2023

3D Cell Cultures Amplify Diffusion Signals

Biophysical models can predict the behavior of cell cultures including 3D cell aggregates (3DCAs), thereby reducing the need for costly and time-consuming experiments. Specifically, mass transfer models enable studying the transport of nutrients, oxygen, signaling molecules, and drugs in 3DCA. These models require the defining of boundary conditions (BC) between the 3DCA and surrounding medium. However, accurately modeling the BC that relates the inner and outer boundary concentrations at the border between the 3DCA and the medium remains a challenge that this paper addresses using both theoretical and experimental methods. The provided biophysical analysis indicates that the concentration of molecules inside boundary is higher than that at the outer boundary, revealing an amplification factor that is confirmed by a particle-based simulator (PBS). Due to the amplification factor, the PBS confirms that when a 3DCA with a low concentration of target molecules is introduced to a culture medium with a higher concentration, the molecule concentration in the medium rapidly decreases. The theoretical model and PBS simulations were used to design a pilot experiment with liver spheroids as the 3DCA and glucose as the target molecule. Experimental results agree with the proposed theory and derived properties. Author summaryThe primary objective of our research was to enable the development of reliable biophysical models for three-dimensional cell aggregates (3DCAs). To achieve this goal, we employed a combination of theoretical and experimental methods to derive and characterize the amplification boundary condition (BC), which represents the relation of inner and outer boundary concentrations at the border between a 3DCA and its surrounding medium. By understanding the amplificaiton BC, we can better comprehend the transport and diffusion processes that occur within 3DCAs. The significance of our research lies in its potential to advance the understanding of 3DCAs and their underlying biophysical processes. This knowledge is crucial for a wide range of applications, including drug design and analysis of drug dosages within tissues. This factor may provide insight into the mechanisms behind tumor development and morphogenesis. In particular, the packed structure of cancer tumors enables them to receive and trap a higher concentration of nutrients and oxygen molecules based on the amplification factor. Thus, this study could contribute to the development of novel approaches to manage and treat cancerous tissues.

biophysics↗

bioRxiv2020

Multi- and transgenerational disruption of maternal behavior and female puberty by Endocrine Disrupting Chemical (EDC) mixture exposure

Female reproductive development and maternal behavior are two intertwined phenotypes centrally controlled by the hypothalamus. Endocrine disrupting chemicals (EDC) can alter these processes especially when animals are exposed during development. We propose the concept that developmental exposure to a low environmentally relevant dose of EDC mixture induces a transgenerational alteration of female rat pubertal timing and ovarian physiology throughout epigenetic reprograming of hypothalamic Kiss1, Esr1 and Oxt1 loci. Such exposure also caused a multigenerational reduction of maternal behavior induced by the loss in hypothalamic dopaminergic signaling. Our results identify the hypothalamic Polycomb Group of epigenetic repressors as actors of this mechanism of transgenerational reproductive disruption. Using a cross-fostering approach, we identified that while the reduction in maternal phenotype was normalized in EDC exposed pups raised by unexposed dams, no reversal of the pubertal phenotype was achieved, suggesting a germline transmission of the reproductive phenotype.

neuroscience↗