Biology subjects

Sonoda, T.

Publications and source records attributed to Sonoda, T..

5 recordsLinked to original sources

bioRxiv2026

Host-like Temperature Unlocks Glucose Uptake and Metabolism in Pathogenic Leptospira

Pathogenic Leptospira transitions between environmental reservoirs and mammalian hosts, expose the bacterium to distinct temperature conditions. Although Leptospira is generally considered to rely its growth primarily on long-chain fatty acids and to have limited capacity to use glucose, whether host-like temperature alters glucose-associated metabolic capacity remains unclear. Here, we used transcriptome-integrated genome-scale metabolic modeling to examine temperature-dependent metabolic states in pathogenic Leptospira. Models contextualized with transcriptomic data from cultures at 37{degrees}C predicted increased flux through glucose transport, glucose phosphorylation, and downstream glucose-associated reactions than it did at 29-30{degrees}C. Similar temperature-dependent predictions were obtained for another pathogenic Leptospira species under in vitro conditions. Consistent with these findings, analysis of leptospires cultivated intraperitoneally in dialysis membrane chambers also predicted enhanced glucose uptake and metabolism under host-temperature conditions. In vitro validation experiments showed increased bacterial uptake or accumulation of a fluorescent glucose analogue, elevated expression of candidate glucose transporter genes, and glucose-dependent enhancement of bacterial growth at 37{degrees}C. Treatment with a glucose degradation pathway inhibitor, 2-deoxy-D-glucose further supported a contribution of glucose-associated processes to proliferation at 37{degrees}C. Together, these findings indicate that pathogenic Leptospira displays condition-dependent glucose uptake and glucose-associated metabolic activity that become apparent at host-like temperature, opposed to glucose-incompetent in an environmental-like temperature. This prediction-driven framework refines the conventional view of Leptospira carbon metabolism and provides a basis for future studies of glucose-associated metabolic capacity during mammalian infection. ImportanceEnvironmental reservoirs play a central role in the transmission of many bacterial pathogens, yet the metabolic mechanisms that enable adaptation to both environmental and host-associated niches remain largely unknown. Using a prediction-driven framework that combines contextualized genome-scale metabolic modeling with multi-omics analyses and experimental validation, we discovered that pathogenic Leptospira activates glucose uptake and metabolism only under host-like conditions. This finding resolves a long-standing misconception arising from studies performed under conventional laboratory conditions and fundamentally revises our understanding of Leptospira physiology. More importantly, our study establishes an integrative systems biology strategy for uncovering condition-dependent metabolic traits that would be difficult to identify experimentally alone, with broad applicability to diverse environmentally transmitted pathogens.

microbiology↗

bioRxiv2026

Soil bacterium Massilia secretes metabolites that promote Leptospira growth

Understanding pathogen metabolism is critical for identifying key functions for drug targeting, establishing effective in vitro experimental systems, etc., particularly for metabolically unique organisms such as Leptospira. Pathogenic Leptospira are thought to infect humans from environmental sources; however, direct isolation from environmental samples remains technically challenging and is not yet well established. Here, we report that a ubiquitous environmental bacterium, Massilia sp., produces metabolites that promote the growth of Leptospira interrogans, encountered through an incidental contamination event, and identified in this study. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis showed demonstrated that cultivating of Massilia sp. in R2A medium resulted in the accumulation of metabolites, including branched-chain amino acid (BCAA) intermediates, compared to fresh medium. By combining genome-scale metabolic modeling with experimental validation using cell-free culture supernatant supplementation assays, we demonstrate that BCAA intermediates, particularly 2-ketoisocaproic acid (4-methyl-2-oxopentanoate; 4MOP), a leucine biosynthetic intermediate produced by Massilia sp., enhance Leptospira growth. To investigate the metabolic role of 4MOP, we incorporated transcriptomic data into a genome-scale metabolic network model to generate condition-specific models. Resulted flux distributions indicated that Leptospira catabolized imported 4MOP to produce acetyl-CoA. Our results reveal a previously unrecognized metabolic interaction where metabolites produced by environmental bacteria support the growth of pathogenic Leptospira, offering mechanistic insight into its metabolic requirement. These findings have implications to understand the environmental persistence of Leptospira through its metabolic dependencies on coexisting microbes, and they also help develop better strategies for this pathogen. ImportancePathogenic Leptospira persist in environmental reservoirs, yet the mechanisms supporting their growth remain poorly defined. Here, we find that metabolites produced by common environmental bacteria, Massilia sp., can promote Leptospira growth, suggesting a previously unrecognized metabolic dependency on coexisting microbes. Importantly, this study indicates that combining genome-scale metabolic modeling with experimental validation provides a useful framework for identifying metabolic interactions that are otherwise difficult to resolve using conventional culture-based approaches. Current strategy may facilitate the systematic identification of growth-supporting metabolites and provide a basis for improving selective cultivation for uncultured or difficult to culture organisms. Determination of growth promoting metabolites advances our understanding of pathogen persistence in natural environments and offers a generalized framework to study metabolically dependent microorganisms.

microbiology↗

bioRxiv2024

Transmission of Mixed Convergent Signals at the Mouse Retinogeniculate Synapse

There are two broad modes of information transfer in the brain: the labeled line model, where neurons relay inputs they receive, and the mixed tuning model, where neurons transform and integrate different inputs. In the visual pathway, information transfer between retinal ganglion cells (RGCs) and the dorsal lateral geniculate nucleus (dLGN) neurons is primarily viewed as a labeled line. However, recent work in mice has demonstrated that different RGC types, encoding distinct visual features, can converge onto a dLGN neuron, raising the fundamental question of whether the dLGN transforms visual information. Using optogenetics we activated distinct RGC populations and assessed spiking output of dLGN neurons by in vivo recordings. We found that visual response properties of dLGN neurons driven by a specific RGC population largely matched properties of the activated RGCs. Furthermore, in vitro dual-opsin experiments demonstrate that strong functional convergence from distinct RGC types rarely occurs. Thus, retinogeniculate information transfer in mice largely adheres to a labeled line model.

neuroscience↗

bioRxiv2024

Experience instructs the refinement of feature-selectivity in the mouse primary visual thalamus

Neurons exhibit selectivity for specific features: a property essential for extracting and encoding relevant information in the environment. This feature-selectivity is thought to be modifiable by experience at the level of the cortex. Here, we demonstrate that selective exposure to a feature during development can instruct the population representation for that feature in the primary visual thalamus. This thalamic plasticity is not simply inherited from the cortex because it is still observed when recordings were performed in the absence of cortical feedback. Moreover, plasticity is blocked in mutant mice that exhibit deficits in retinogeniculate refinement, indicating that alterations in feature-selectivity are a direct result of changes in feedforward connectivity. These experience-dependent changes persist into older ages--highlighting the importance of this developmental period in shaping population coding in the thalamus. Our results show that salient environmental features are hard-wired into thalamic circuits during a discrete developmental window.

neuroscience↗

bioRxiv2022

Melanopsin activates divergent phototransduction pathways in ipRGC subtypes

Melanopsin signaling within ipRGC subtypes impacts a broad range of behaviors from circadian photoentrainment to conscious visual perception. Yet, how melanopsin phototransduction within M1-M6 ipRGC subtypes impacts cellular signaling to drive diverse behaviors is still largely unresolved. The identity of the phototransduction channels in each subtype is key to understanding this central question but has remained controversial. In this study, we resolve two opposing models of M4 phototransduction, demonstrating that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dispensable for this process and providing support for a model involving melanopsin-dependent potassium channel closure and canonical transient receptor potential (TRPC) channel opening. Surprisingly, we find that HCN channels are likewise dispensable for M2 phototransduction, contradicting the current model. We instead show that in M2 phototransduction, TRPC channels act in conjunction with T-type voltage-gated calcium channels, a novel melanopsin phototransduction target. Collectively, this work resolves key discrepancies in our understanding of ipRGC phototransduction pathways in multiple subtypes and adds to mounting evidence that ipRGC subtypes employ diverse phototransduction cascades to fine-tune cellular responses for downstream behaviors.

neuroscience↗