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Biology subjects

Fontaine, S.

Publications and source records attributed to Fontaine, S..

5 recordsLinked to original sources

Long lasting non-cellular reactions in sterile soils recapitulates most of the intermediates of the Krebs cycle

Over the past decade, chemical evidence has emerged that non-enzymatic metabolic pathways, such as the Krebs cycle, may have existed before cellular life on the primitive Earth. However, the question of whether non-cellular reactions analogous to cell respiration metabolism are still "active" in todays biosphere and whether they contribute to CO2 emissions in contemporary ecosystems remains open. In the present study, we investigated the long-term fate (> 6 months) of organic substrates supplied in sterilised soils in which cell life was not detectable. Through a series of analytical studies performed on the water-extractable fraction of soil exometabolites using chromatography, mass spectrometry and isotope labelling, we demonstrate that sterile soil matrix incubated with [13C6]-glucose and [13C6]-citrate can spontaneously generate intermediates of the Krebs cycle, alongside by-products such as acetate and formate. These findings support the hypothesis that extracellular metabolisms (EXOMETs) form a network of non-cellular reactions resembling metabolic pathways involved in aerobic respiration and anaerobic fermentation of cells. This research not only provides insights into the chemical continuity between chemistry and biochemistry but also raises questions about the implications of non-cellular pathways for soil ecosystem functioning and carbon fluxes in the contemporary biosphere.

biochemistry↗

Non-living respiration: another breath in the soil?

The present study challenges the traditional view that respiration of organic carbon to CO2 is exclusively an intracellular process, revealing that organic compound respiration can occur spontaneously in an extracellular context in soils. Using 1H nuclear magnetic resonance spectroscopy to analyse the dynamics of the sterile soil exometabolomes alongside C-CO2 flux analyses and sterile soil fuel cells, we show that soil catalysts facilitate a diverse array of substrate-driven reactions, leading to the complete oxidation of organic compounds to CO2 with O2 consumption. Our results indicate that soil particles are capable of transferring electrons from substrates to the final acceptor, sustaining metabolic processes independently of living cells. Notably, some soil catalysts and induced respiration remain stable for over six years. Our results support the coexistence of cellular and non-cellular metabolic pathways in soil respiration.

ecology↗

ADAPT: Analysis of Microbiome Differential Abundance by Pooling Tobit Models

Microbiome differential abundance analysis remains a challenging problem despite multiple methods proposed in the literature. The excessive zeros and compositionality of metagenomics data are two main challenges for differential abundance analysis. We propose a novel method called "analysis of differential abundance by pooling Tobit models" (ADAPT) to overcome these two challenges. ADAPT uniquely treats zero counts as left-censored observations to facilitate computation and enhance interpretation. ADAPT also encompasses a theoretically justified way of selecting non-differentially abundant microbiome taxa as a reference for hypothesis testing. We generate synthetic data using independent simulation frameworks to show that ADAPT has more consistent false discovery rate control and higher statistical power than competitors. We use ADAPT to analyze 16S rRNA sequencing of saliva samples and shotgun metagenomics sequencing of plaque samples collected from infants in the COHRA2 study. The results provide novel insights into the association between the oral microbiome and early childhood dental caries.

bioinformatics↗

Vegetative stage and soil horizon respectively determine direction and magnitude of rhizosphere priming effects in contrasting treeline soils

O_LITreelines in high latitudes and high altitudes are considered sentinels of global change. This manifests in accelerated encroachment of trees and shrubs and enhanced plant productivity, with currently unknown implications for the carbon balance of these biomes. Given the large soil organic carbon stocks in many treeline soils, we here wondered whether introducing highly productive plants would accelerate carbon cycling through rhizosphere priming effects and if certain soils would be more vulnerable to carbon loss from positive priming than others. C_LIO_LITo test this, organic and mineral soils were sampled above and below treelines in the Swedish sub-arctic and the Peruvian Andes. A greenhouse experiment was then performed to quantify plant-induced changes in soil mineralisation rates (rhizosphere priming effect) and new C formation using natural abundance labelling and the C4-species Cynodon dactylon. Several environmental, plant, soil and microbial parameter were monitored during the experiment to complement the observations on soil C cycling. C_LIO_LIPriming was predominantly positive at the beginning of the experiment, then systematically decreased in all soils during the plant growth season to be mostly negative at the end of the experiment at plant senescence. Independent of direction of priming, the magnitude of priming was always greater in organic than in corresponding mineral soils, which was best explained by the higher C contents of these soils. Integrated over the entire study period, the overall impact of priming (positive and negative) on the soil C balance was mostly negligible. Though, net soil C loss was observed in organic soils from the sub-arctic tundra in Sweden. C_LIO_LIMost notably, positive and negative priming effects were not mutually exclusive, rather omnipresent across ecosystems, depending on sampling time. The direction of priming seems to be fluctuating with plant productivity, rhizosphere carbon inputs and nutrient uptake. This highlights the need for integrative long-term studies if we aim to understand priming effects at ecosystem scale and greenhouse and laboratory studies must be validated in situ to enable reliable ecological upscaling. C_LI

ecology↗

Highly potent anti-SARS-CoV-2 multi-DARPin therapeutic candidates

Globally accessible therapeutics against SARS-CoV-2 are urgently needed. Here, we report the generation of the first anti-SARS-CoV-2 DARPin molecules with therapeutic potential as well as rapid large-scale production capabilities. Highly potent multivalent DARPin molecules with low picomolar virus neutralization efficacies were generated by molecular linkage of three different monovalent DARPin molecules. These multivalent DARPin molecules target various domains of the SARS-CoV-2 spike protein, thereby limiting possible viral escape. Cryo-EM analysis of individual monovalent DARPin molecules provided structural explanations for the mode of action. Analysis of the protective efficacy of one multivalent DARPin molecule in a hamster SARS-CoV-2 infection model demonstrated a significant reduction of pathogenesis. Taken together, the multivalent DARPin molecules reported here, one of which has entered clinical studies, constitute promising therapeutics against the COVID-19 pandemic.

immunology↗