Metabolomics. 2024 Dec 30;21(1):14. doi: 10.1007/s11306-024-02205-z.

ABSTRACT

INTRODUCTION: Burkholderia thailandensis E264 is a non-pathogenic soil bacterium that produces rhamnolipids (RLs), which are utilised in various fields. Although studies have illustrated changes in RLs congeners in response to environmental factors, studies on the influence of temperature on the RLs congeners produced by B. thailandensis E264 are scarce.

OBJECTIVE: It was hypothesised that RL congeners will be distributed differently at different temperature, which caused the produced RL to have different properties. This brought about the idea of a tailored production of RL for specific application through temperature control. Thus, this study aimed to investigate the distribution of RLs congeners by B. thailandensis E264 in response to different temperatures.

METHODOLOGY: B. thailandensis E264 was grown at three different temperatures (25 °C, 30 °C, and 37 °C) for nine days and subjected to metabolomic analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS).

RESULTS: The findings indicated that temperature significantly affected the metabolomic distribution of B. thailandensis E264, with mono-rhamno-mono-lipid and mono-rhamno-di-lipid being the predominant metabolites at 37 °C and 30 °C, with relative abundances of 64.1% and 65.3%, respectively. In comparison, di-rhamno-di-lipid was detected at 25 °C with an overall relative abundance of 77.7%.

CONCLUSION: This investigation showed that changing the cultivation temperature of the non-pathogenic B. thailandensis E264 produces diverse rhamnolipid congeners, which could enable the targeted synthesis of specific RLs for various applications and increase the market value of biosurfactants.

PMID:39738744 | DOI:10.1007/s11306-024-02205-z

Cell Biol Toxicol. 2024 Dec 30;41(1):20. doi: 10.1007/s10565-024-09978-y.

ABSTRACT

Environmental chemicals and toxins are known to impact human health and contribute to cancer developments. Among these, genotoxins induce genetic mutations critical for cancer initiation. In the liver, proliferation serves not only as a compensatory mechanism for tissue repair but also as a potential risk factor for the progression of premalignant lesions. The role of Human Liver DnaJ-Like Protein (DNAJB4/HLJ1), a stress-responsive heat shock protein 40, in genotoxin-induced liver carcinogenesis remains unexplored. Using whole-genome transcriptomic analysis, we demonstrate that HLJ1 deficiency in mice results in altered gene signatures enriched in pathways associated with chemically induced liver cancer and IL-6/STAT3 signaling activation. Employing diethylnitrosamine (DEN) as a carcinogen, we further reveal that STAT3 and H2AX phosphorylation induced by short-term DEN treatment are amplified in HLJ1-deficient mice. In long-term DEN experiments, HLJ1 deletion enhances tumor proliferation and progression, accompanied by pronounced STAT3 phosphorylation in normal tissues rather than in tumor regions. The tumor-suppressive role of peritumoral HLJ1 is validated through the transplantation of HLJ1-wildtype B16F1 and LLC cancer cell lines into syngeneic HLJ1-deficient mice, which exhibits an augmented tumorigenic phenotype compared to wildtype controls. This study uncovers a previously unrecognized role of HLJ1 in suppressing liver carcinogenesis via the downregulation of STAT3 signaling in peritumoral normal cells. These findings suggest that HLJ1 reinforcement represents a promising strategy for liver cancer treatment and prevention.

PMID:39738726 | DOI:10.1007/s10565-024-09978-y

Sci Rep. 2024 Dec 30;14(1):31839. doi: 10.1038/s41598-024-83172-2.

ABSTRACT

Meal sorting in mosquitoes is a phenomenon whereby ingested blood and sugar meals are directed to different destinations in the alimentary canal. We undertake a systematic analysis and show that entry of blood in the midgut is influenced by blood components, temperature, and feeding mode, while sugar solutions are directed to the crop in a dose-dependent manner. Sweet and nutritive sugars, like sucrose and maltose, enter the crop more efficiently compared to non-sweet or non-nutritive sugars. Additionally, the robustness of meal sorting declines with mosquito age and is compromised in mutants of candidate thermoreceptors. Proper blood meal sorting is crucial for optimal egg production, as disruption of this process by adding sucrose results in reduced fecundity. Furthermore, certain amino acids essential for vitellogenesis are preferentially directed to the midgut. Our findings provide new insights into the meal sorting mechanism, with implications for mosquito reproduction and vectorial capacity.

PMID:39738426 | DOI:10.1038/s41598-024-83172-2

Sci Rep. 2024 Dec 30;14(1):31710. doi: 10.1038/s41598-024-82056-9.

ABSTRACT

Global health is affected by viral, bacterial, and fungal infections that cause chronic and often fatal diseases. Identifying novel antimicrobials through innovative methods that are active against human pathogens will create a new, necessary pipeline for chemical discovery and therapeutic development. Our goal was to determine whether algal production systems represent fertile ground for discovery of antibiotics and antifungals. To this end, we collected high-biomass algal-bacterial samples from outdoor mass cultivation systems, 18-L outdoor algal open cultures mesocosms, and non-axenic laboratory samples. We also cultivated 33 marine bacterial isolates for chemical extraction. Ultimately, we filtered, concentrated, extracted, and screened 77 chemically-complex mixtures using a conventional agar-based microbial growth inhibition assay against three microbes: Escherichia coli, Bacillus subtilis, and Candida albicans. We discovered that 23 of our chemical extracts (almost one-third of the chemical samples tested) exhibited some degree of growth inhibition toward B. subtilis and/or C. albicans. Our work here demonstrates the feasibility and potential of isolating bioactive natural products from high-biomass algal-bacterial samples from algal mass cultivation systems.

PMID:39738328 | DOI:10.1038/s41598-024-82056-9

Nat Commun. 2024 Dec 30;15(1):10858. doi: 10.1038/s41467-024-55222-w.

ABSTRACT

Sponges harbour complex microbiomes and as ancient metazoans and important ecosystem players are emerging as powerful models to understand the evolution and ecology of symbiotic interactions. Metagenomic studies have previously described the functional features of sponge symbionts, however, little is known about the metabolic interactions and processes that occur under different environmental conditions. To address this issue, we construct here constraint-based, genome-scale metabolic networks for the microbiome of the sponge Stylissa sp. Our models define the importance of sponge-derived nutrients for microbiome stability and discover how different organic inputs can result in net heterotrophy or autotrophy of the symbiont community. The analysis further reveals the key role that a newly discovered bacterial taxon has in cross-feeding activities and how it dynamically adjusts with nutrient inputs. Our study reveals insights into the functioning of a sponge microbiome and provides a framework to further explore and define metabolic interactions in holobionts.

PMID:39738126 | DOI:10.1038/s41467-024-55222-w

Nat Commun. 2024 Dec 30;15(1):10888. doi: 10.1038/s41467-024-55248-0.

ABSTRACT

Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume. Diverse antigens, mRNAs, neurotransmitters, and post-translational modifications are well-preserved and simultaneously visualized. INSIHGT also allows multi-round, highly multiplexed 3D molecular probing and is compatible with downstream traditional histology and nucleic acid sequencing. With INSIHGT, we map undescribed podocyte-to-parietal epithelial cell microfilaments in mouse glomeruli and neurofilament-intensive inclusion bodies in the human cerebellum, and identify NPY-proximal cell types defined by spatial morpho-proteomics in mouse hypothalamus. We anticipate that INSIHGT can form the foundations for 3D spatial multi-omics technology development and holistic systems biology studies.

PMID:39738072 | DOI:10.1038/s41467-024-55248-0

Nat Commun. 2024 Dec 30;15(1):10924. doi: 10.1038/s41467-024-55359-8.

ABSTRACT

Thiamine and pyridoxine are essential B vitamins that serve as enzymatic cofactors in energy metabolism, protein and nucleic acid biosynthesis, and neurotransmitter production. In humans, thiamine transporters SLC19A2 and SLC19A3 primarily regulate cellular uptake of both vitamins. Genetic mutations in these transporters, which cause thiamine and pyridoxine deficiency, have been implicated in severe neurometabolic diseases. Additionally, various prescribed medicines, including metformin and fedratinib, manipulate thiamine transporters, complicating the therapeutic effect. Despite their physiological and pharmacological significance, the molecular underpinnings of substrate and drug recognition remain unknown. Here we present ten cryo-EM structures of human thiamine transporters SLC19A3 and SLC19A2 in outward- and inward-facing conformations, complexed with thiamine, pyridoxine, metformin, fedratinib, and amprolium. These structural insights, combined with functional characterizations, illuminate the translocation mechanism of diverse chemical entities, and enhance our understanding of drug-nutrient interactions mediated by thiamine transporters.

PMID:39738067 | DOI:10.1038/s41467-024-55359-8

Nat Commun. 2024 Dec 30;15(1):10842. doi: 10.1038/s41467-024-55187-w.

ABSTRACT

Antibody-mediated protection against pathogens is crucial to a healthy life. However, the recent SARS-CoV-2 pandemic has shown that pre-existing comorbid conditions including kidney disease account for compromised humoral immunity to infections. Individuals with kidney disease are not only susceptible to infections but also exhibit poor vaccine-induced antibody response. Using multiple mouse models of kidney disease, we demonstrate that renal dysfunction inhibits germinal center (GC) response against T-dependent antigens. GC B cells exhibit increased apoptosis in kidney disease. Uremic toxin hippuric acid drives loss of mitochondrial membrane potential, leading to increased apoptosis of GC B cells in a G-protein-coupled receptor 109A dependent manner. Finally, GC B cells and antibody titer are diminished in mice with kidney disease following influenza virus infection, a major cause of mortality in individuals with renal disorders. These results provide a mechanistic understanding of how renal dysfunction suppresses humoral immunity in patients with kidney disease.

PMID:39738044 | DOI:10.1038/s41467-024-55187-w

ACS Infect Dis. 2024 Dec 31. doi: 10.1021/acsinfecdis.4c00701. Online ahead of print.

ABSTRACT

New World alphaviruses, including Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that cause disease in humans. These viruses are endemic to the western hemisphere, and disease in humans may lead to encephalitis and long-term neurological sequelae. There are currently no FDA-approved vaccines or antiviral therapeutics available for the prevention or treatment of diseases caused by these viruses. The alphavirus nonstructural protein 2 (nsP2) functions as a protease, which is critical for the establishment of a productive viral infection by enabling accurate processing of the nsP123 polyprotein. Owing to the essential role played by nsP2 in the alphavirus infectious process, it is also a valuable therapeutic target. In this article, we report the synthesis and evaluation of novel small molecule inhibitors that target the alphavirus nsP2 protease via a covalent mode of action. The two lead compounds demonstrated robust inhibition of viral replication in vitro. These inhibitors interfered with the processing of the nsP123 polyprotein as determined using VEEV TC-83 as a model pathogen and are active against EEEV and WEEV. The compounds were found to be nontoxic in two different mouse strains and demonstrated antiviral activity in a VEEV TC-83 lethal challenge mouse model. Cumulatively, the outcomes of this study provide a compelling rationale for the preclinical development of nsP2 protease inhibitors as direct-acting antiviral therapeutics against alphaviruses.

PMID:39737550 | DOI:10.1021/acsinfecdis.4c00701

Front Immunol. 2024 Dec 16;15:1508110. doi: 10.3389/fimmu.2024.1508110. eCollection 2024.

ABSTRACT

The COVID-19 pandemic has significantly impacted global health, especially in vulnerable populations like kidney transplant recipients (KTRs). Recently, mass spectrometry-based proteomics has emerged as a powerful tool to shed light on a broad spectrum of dysregulated biological processes in KTRs with COVID-19. In this study, we prospectively collected blood samples from 17 COVID-19-positive KTRs and 10 non-infected KTRs between May and September 2020. Using tandem mass tag-based quantitative proteomics, we analyzed peripheral blood mononuclear cells (PBMCs), plasma protein biomarkers, and lymphocyte counts, followed by bioinformatics analysis. Our results revealed significant proteomic alterations in COVID-19-infected KTRs, particularly in pathways related to glycolysis, glucose metabolism, and neutrophil degranulation. Additionally, we observed an altered immune response characterized by elevated cytokines and decreased lymphocyte counts. Notably, KTRs with AKI exhibited worse clinical outcomes, including higher rates of ICU admission and mechanical ventilation. Comparative analysis of PBMC proteomic profiles between AKI and non-AKI patients identified distinct immune-related pathways, with AKI patients showing marked changes in innate immune responses, particularly neutrophil degranulation. Furthermore, we observed a negative correlation between T cell counts and neutrophil degranulation, suggesting a role for immune dysregulation in COVID-19. Our findings provide critical insights into the immune and metabolic responses in COVID-19-infected KTRs, especially those with AKI, highlighting the need for focused research and therapeutic strategies targeting immune dysregulation in this high-risk population.

PMID:39737170 | PMC:PMC11683116 | DOI:10.3389/fimmu.2024.1508110

Front Vet Sci. 2024 Dec 16;11:1486635. doi: 10.3389/fvets.2024.1486635. eCollection 2024.

ABSTRACT

INTRODUCTION: Small mammals, especially rodents and bats, are known reservoirs of zoonotic viruses, but little is known about the viromes of insectivorous species including hedgehogs (order Eulipotyphla), which often live near human settlements and come into contact with humans.

METHODS: We used high-throughput sequencing and metaviromic analysis to describe the viromes of 21 hedgehogs (Erinaceus sp.) sampled from summer 2022 to spring 2023. We captured 14 active animals from the wild (seven in European Russia and the other seven in Central Siberia). The remaining 7 animals were hibernating in captivity (captured in European Russia before the experiment).

RESULTS AND DISCUSSION: The diversity of identified viral taxa as well as the total number of reads classified as viral was high in all active animals (up to eight different viral families per animal), but significantly lower in hibernating animals (zero or no more than three different viral families per animal). The present study reports, for the first time, betacoronaviruses and mammasrenaviruses in hedgehogs from Russia. Erinaceus coronaviruses (EriCoVs) were found in 4 of 7 active animals captured in the wild, in European Russia, making it is the easiest finding of EriCoVs in Europe. One animal was found to carry of two different EriCoVs. Both strains belong to the same phylogenetic clade as other coronaviruses from European hedgehogs. Pairwise comparative analysis suggested that one of these two strains arose by recombination with an unknown coronavirus, since all of identified SNPs (n = 288) were found only in the local genome region (the part of ORF1b and S gene). The novel mammarenaviruses (EriAreVs) were detected in 2 out of 7 active and in 2 out of 7 hibernating animals from the European Russia. Several complete L and S segments of EriAreVs were assembled. All identified EriAreVs belonged to the same clade as the recently described MEMV virus from Hungarian hedgehogs. As the hibernating hedgehogs were positive for EriAreVs when kept in controlled conditions without contact with each other, we suggest the possibility of persistent arenavirus infection in hedgehogs, but further experiments are needed to prove this.

PMID:39736935 | PMC:PMC11683907 | DOI:10.3389/fvets.2024.1486635

ISME Commun. 2024 Dec 4;4(1):ycae153. doi: 10.1093/ismeco/ycae153. eCollection 2024 Jan.

ABSTRACT

A comprehensive understanding of microbial community dynamics is fundamental to the advancement of environmental microbiology, human health, and biotechnology. Metaproteomics, defined as the analysis of all proteins present within a microbial community, provides insights into these complex systems. Microbial adaptation and activity depend to an important extent on newly synthesized proteins (nP), however, the distinction between nP and bulk proteins is challenging. The application of BONCAT with click chemistry has demonstrated efficacy in the enrichment of nP in pure cultures for proteomics. However, the transfer of this technique to microbial communities and metaproteomics has proven challenging and thus it has not not been used on microbial communities before. To address this, a new workflow with efficient and specific nP enrichment was developed using a laboratory-scale mixture of labelled Escherichia coli and unlabeled yeast. This workflow was then successfully applied to an anaerobic microbial community with initially low bioorthogonal non-canonical amino acid tagging efficiency. A substrate shift from glucose to ethanol selectively enriched nP with minimal background. The identification of bifunctional alcohol dehydrogenase and a syntrophic interaction between an ethanol-utilizing bacterium and two methanogens (hydrogenotrophic and acetoclastic) demonstrates the potential of metaproteomics targeting nP to trace microbial activity in complex microbial communities.

PMID:39736848 | PMC:PMC11683836 | DOI:10.1093/ismeco/ycae153

BMC Biol. 2024 Dec 31;22(1):301. doi: 10.1186/s12915-024-02096-5.

ABSTRACT

BACKGROUND: Molecular interactions between proteins and their ligands are important for drug design. A pharmacophore consists of favorable molecular interactions in a protein binding site and can be utilized for virtual screening. Pharmacophores are easiest to identify from co-crystal structures of a bound protein-ligand complex. However, designing a pharmacophore in the absence of a ligand is a much harder task.

RESULTS: In this work, we develop a deep learning method that can identify pharmacophores in the absence of a ligand. Specifically, we train a CNN model to identify potential favorable interactions in the binding site, and develop a deep geometric Q-learning algorithm that attempts to select an optimal subset of these interaction points to form a pharmacophore. With this algorithm, we show better prospective virtual screening performance, in terms of F1 scores, on the DUD-E dataset than random selection of ligand-identified features from co-crystal structures. We also conduct experiments on the LIT-PCBA dataset and show that it provides efficient solutions for identifying active molecules. Finally, we test our method by screening the COVID moonshot dataset and show that it would be effective in identifying prospective lead molecules even in the absence of fragment screening experiments.

CONCLUSIONS: PharmRL addresses the need for automated methods in pharmacophore design, particularly in cases where a cognate ligand is unavailable. Experimental results demonstrate that PharmRL generates functional pharmacophores. Additionally, we provide a Google Colab notebook to facilitate the use of this method.

PMID:39736736 | DOI:10.1186/s12915-024-02096-5

Breast Cancer Res. 2024 Dec 30;26(1):190. doi: 10.1186/s13058-024-01951-1.

ABSTRACT

Autophagy, a crucial process in cancer, is closely intertwined with both tumor progression and drug resistance development. However, existing methods used to assess autophagy activity often pose invasiveness and time-related constraints, limiting their applicability in preclinical drug investigations. In this study, we developed a non-invasive autophagy detection system (NIADS-autophagy, also called G-cleave LC3B biosensor) by integrating a split-luciferase-based biosensor with an LC3B cleavage sequence, which swiftly identified classic autophagic triggers, such as Earle's Balanced Salt Solution and serum deprivation, through protease-mediated degradation pathways. The specificity of G-cleave LC3B biosensor was confirmed via CRISPR gene editing of pivotal autophagy regulator ATG4B, yielding diminished luciferase activity in MDA-MB-231 breast cancer cells. Notably, the G-cleave LC3B biosensor exhibited strong concordance with established autophagy metrics, encompassing LC3B lipidation, SQSTM1 degradation, and puncta accumulation analysis. To underscore the usage potential of the G-cleave LC3B biosensor, we discovered that resveratrol acts as a synergistic enhancer by significantly potentiating apoptosis in MDA-MB-231 cells when combined with doxorubicin treatment. Overall, the luminescence-based G-cleave LC3B biosensor presents a rapid and dependable avenue for determining autophagy activity, thereby facilitating high-throughput assessment of promising autophagy-associated anti-cancer therapies across diverse malignancies.

PMID:39736723 | DOI:10.1186/s13058-024-01951-1

Genome Biol. 2024 Dec 30;25(1):322. doi: 10.1186/s13059-024-03458-6.

ABSTRACT

Spatial epigenomic technologies enable simultaneous capture of spatial location and chromatin accessibility of cells within tissue slices. Identifying peaks that display spatial variation and cellular heterogeneity is the key analytic task for characterizing the spatial chromatin accessibility landscape of complex tissues. Here, we propose an efficient and iterative model, Descart, for spatially variable peaks identification based on the graph of inter-cellular correlations. Through the comprehensive benchmarking, we demonstrate the superiority of Descart in revealing cellular heterogeneity and capturing tissue structure. Utilizing the graph of inter-cellular correlations, Descart shows its potential to denoise data, identify peak modules, and detect gene-peak interactions.

PMID:39736655 | DOI:10.1186/s13059-024-03458-6

J Am Chem Soc. 2024 Dec 30. doi: 10.1021/jacs.4c14650. Online ahead of print.

ABSTRACT

PROTACs have emerged as a therapeutic modality for the targeted degradation of proteins of interest (POIs). Central to PROTAC technology are the E3 ligase recruiters, yet only a few of them have been identified due to the lack of ligandable pockets in ligases, especially among single-subunit ligases. We propose that binders of partner proteins of single-subunit ligases could be repurposed as new ligase recruiters. MDM2 is a single-subunit ligase overexpressed in tumors. Nucleolin (NCL) is an MDM2 partner protein that displays a similar tumor-specific overexpression pattern and nuclear-cytoplasmic shuttling role to MDM2. Furthermore, NCL is selectively translocated on the tumor cell surface, where it acts as an internalization receptor for its binders. We reveal that the NCL-binding Oridonin (Ori), a natural ent-kaurene diterpenoid, is capable of recruiting MDM2 by employing NCL as a molecular bridge. We design Ori-based PROTACs for modulating oncogenic POIs, including BRD4 and EGFR. These PROTACs direct the assembly of MDM2-NCL-PROTAC-POI complexes to induce proteasomal degradation of POIs and tumor shrinkage. In addition to its role as a ligase engaged by PROTACs, MDM2, along with its homologue MDMX, plays a nonredundant function in inhibiting p53 activity. Dual inhibition of MDM2/X is proposed as a promising antitumor strategy. We demonstrate that Ori also recruits MDMX in an NCL-dependent manner. Ori-based homo-PROTACs induce MDM2/X dual degradation and attenuate tumor progression. Our findings prove the feasibility of repurposing the binders of ligase partner proteins as new ligase recruiters in PROTACs and highlight the potential of Ori as an MDM2/X recruiter.

PMID:39736140 | DOI:10.1021/jacs.4c14650

Front Microbiol. 2024 Dec 13;15:1492179. doi: 10.3389/fmicb.2024.1492179. eCollection 2024.

ABSTRACT

Nicotinamide mononucleotide (NMN), one of the crucial precursors of nicotinamide adenine dinucleotide, has garnered considerable interest for its pharmacological and anti-aging effects, conferring potential health and economic benefits for humans. Lactic acid bacteria (LAB) are one of the most important probiotics, which is commonly used in the dairy industry. Due to its probiotic properties, it presents an attractive platform for food-grade NMN production. LAB have also been extensively utilized to enhance the functional properties of pharmaceuticals and cosmetics, making them promising candidates for large-scale up synthesis of NMN. This review provides an in-depth analysis of various metabolic engineering strategies, including enzyme optimization, pathway rewiring, and fermentation process enhancements, to increase NMN yields in LAB. It explores both CRISPR/Cas9 and traditional methods to manipulate key biosynthetic pathways. In particular, this study discussed future research directions, emphasizing the application of synthetic biology, systems biology, and AI-driven optimization to further enhance NMN production. It provides invaluable insights into developing scalable and industrially relevant processes for NMN production to meet the growing market demand.

PMID:39735184 | PMC:PMC11681623 | DOI:10.3389/fmicb.2024.1492179

Fundam Res. 2022 Dec 26;4(6):1674-1687. doi: 10.1016/j.fmre.2022.12.009. eCollection 2024 Nov.

ABSTRACT

Making time-series forecasting in a robust way is a difficult task only based on the observed data of a nonlinear system. In this work, a neural network computing framework, the spatiotemporal information conversion machine (STICM), was developed to efficiently and accurately render a forecasting of a time series by employing a spatial-temporal information (STI) transformation. STICM combines the advantages of both the STI equation and the temporal convolutional network, which maps the high-dimensional/spatial data to the future temporal values of a target variable, thus naturally providing the forecasting of the target variable. From the observed variables, the STICM also infers the causal factors of the target variable in the sense of Granger causality, which are in turn selected as effective spatial information to improve the robustness of time-series forecasting. The STICM was successfully applied to both benchmark systems and real-world datasets, all of which show superior and robust performance in time-series forecasting, even when the data were perturbed by noise. From both theoretical and computational viewpoints, the STICM has great potential in practical applications in artificial intelligence or as a model-free method based only on the observed data, and also opens a new way to explore the observed high-dimensional data in a dynamical manner for machine learning.

PMID:39734521 | PMC:PMC11670686 | DOI:10.1016/j.fmre.2022.12.009

Sci Rep. 2024 Dec 28;14(1):31374. doi: 10.1038/s41598-024-82833-6.

ABSTRACT

Enhancing crops productivity to ensure food security is one of the major challenges encountering agriculture today. A promising solution is the use of biostimulants, which encompass molecules that enhance plant fitness, growth, and productivity. The regulatory metabolite zaxinone and its mimics (MiZax3 and MiZax5) showed promising results in improving the growth and yield of several crops. Here, the impact of their exogenous application on soil and rice root microbiota was investigated. Plants grown in native paddy soil were treated with zaxinone, MiZax3, and MiZax5 and the composition of bacterial and fungal communities in soil, rhizosphere, and endosphere at the tillering and the milky stage was assessed. Furthermore, shoot metabolome profile and nutrient content of the seeds were evaluated. Results show that treatment with zaxinone and its mimics predominantly influenced the root endosphere prokaryotic community, causing a partial depletion of plant-beneficial microbes at the tillering stage, followed by a recovery of the prokaryotic community structure during the milky stage. Our study provides new insights into the role of zaxinone and MiZax in the interplay between rice and its root-associated microbiota and paves the way for their practical application in the field as ecologically friendly biostimulants to enhance crop productivity.

PMID:39732893 | DOI:10.1038/s41598-024-82833-6

Cell Host Microbe. 2024 Dec 18:S1931-3128(24)00447-5. doi: 10.1016/j.chom.2024.12.002. Online ahead of print.

ABSTRACT

Gastrointestinal colonization by Clostridioides difficile is common in healthcare settings and ranges in presentation from asymptomatic carriage to lethal C. difficile infection (CDI). We used a systems biology approach to investigate why patients colonized with C. difficile have a range of clinical outcomes. Microbiota humanization of germ-free mice with fecal samples from toxigenic C. difficile carriers revealed a spectrum of virulence among clinically prevalent clade 1 lineages and identified candidate taxa, including Blautia, as markers of stable colonization. Using gnotobiotic mice engrafted with defined human microbiota, we validated strain-specific CDI severity across clade 1 strains isolated from patients. Mice engrafted with a community broadly representative of colonized patients were protected from severe disease across all strains without suppression of C. difficile colonization. These results underline the capacity of gut community structure to attenuate a diversity of pathogenic strains without inhibiting colonization, providing insight into determinants of stable C. difficile carriage.

PMID:39731916 | DOI:10.1016/j.chom.2024.12.002