Garnier, P. | bioRxiv Science

bioRxiv2021

Queuine, a bacterial derived hypermodified nucleobase, shows protection in in vitro models of neurodegeneration

Growing evidence suggests that human gut bacteria, comprising the microbiome that communicates with the brain through the so-called gut-brain-axis, are linked to neurodegenerative disorders. Imbalances in the microbiome of Parkinsons disease (PD) and Alzheimers disease (AD) patients have been detected in several studies. Queuine is a hypermodified nucleobase enriched in the brain and exclusively produced by bacteria and salvaged by humans through their gut epithelium. Queuine replaces guanine at the wobble position of tRNAs with GUN anticodons and promotes efficient cytoplasmic and mitochondrial mRNA translation. To elucidate whether queuine could facilitate protein folding and prevent aggregation and mitochondrial defects, hallmarks of neurodegenerative disorders, we tested the effect of chemically synthesized queuine, STL-101, in several in vitro models of neurodegeneration. Treatment with STL-101 led to increased neuronal survival as well as a significant decrease in hyper-phosphorylated alpha-synuclein, a marker of alpha-synuclein aggregation in a PD model and a decrease in tau hyperphosphorylation in an AD model. Our work has identified a new role for queuine in neuroprotection uncovering a therapeutic potential for STL-101 in neurological disorders.

neuroscience↗

bioRxiv2020

Bacterial density as an unexpected factor regulating decomposition by soil oligotrophs

Bacterial decomposition of organic matter in soils is generally believed to be mainly controlled by the access bacteria have to their substrate. The influence of bacterial traits on this control has, however, received little attention. Here, we develop a bioreactive transport model to screen the interactive impacts of dispersion and bacterial traits on mineralization. We compare the model results with two sets of previously performed cm-scale soil-core experiments in which the mineralization of the pesticide 2,4-D was measured under well-controlled initial distributions and transport conditions. Bacterial dispersion away from the initial substrate location induced a significant increase in 2,4-D mineralization, revealing the existence of a regulation of mineralization by the bacterial decomposer density, in addition to the dilution of substrate. This regulation of degradation by density becomes dominant for bacteria with an efficient uptake of substrate at low substrate concentrations (a common feature of oligotrophs). The model output suggests that the distance between bacteria adapted to oligotrophic environments is a stronger regulator of degradation than the distance between these bacteria and the substrate initial location. Such oligotrophs, commonly found in soils, compete with each other for substrate even at remarkably low population densities. The ratio-dependent Contois growth model, which includes a density regulation in the expression of the uptake efficiency, provide a more versatile representation than the substrate-dependent Monod model in these conditions. In view of their strong interactions, bioreactive and transport processes cannot be handled independently but should be integrated, in particular when reactive processes of interest are carried out by oligotrophs. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/384735v3_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@187f3f4org.highwire.dtl.DTLVardef@a14d46org.highwire.dtl.DTLVardef@1d8362aorg.highwire.dtl.DTLVardef@1cc40f8_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- The impact of spatial distributions on decomposition depends on bacterial traits - Decomposition can be reduced by competition between bacteria even at low densities - Bacterial density regulation counterbalances substrate accessibility regulation - Regulation of decomposition by bacterial density is more acute for oligotrophs

ecology↗