Biology subjects

Zhao, Q.

Publications and source records attributed to Zhao, Q..

At least 127 records · Page 7Linked to original sources

bioRxiv2024

Multiomic Screening Unravels the Immunometabolic Signatures and Drug Targets of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a significant cause of visual impairment in the aging population, with the pathophysiology driven by a complex interplay of genetics, environmental influences and immunometabolic factors. These immunometabolic mechanisms, in particular, those distinguishing between the dry and wet forms of AMD, remain incompletely understood. Utilizing an integrated multiomic approach, incorporating Mendelian Randomization (MR) and single-cell RNA sequencing (scRNA-seq), we have effectively delineated distinct immunometabolic pathways implicated in the development of AMD. Our comprehensive analysis indicates that the androgen-IL10RA-CD16+ monocyte axis could protect against wet AMD. We have also identified several immune and metabolic signatures unique to each AMD subtype, with TNF and Notch signaling pathways being central to disease progression. Furthermore, our analysis, leveraging expression Quantitative Trait Loci (eQTLs) from the Genotype-Tissue Expression (GTEx) project coupled with MR, have highlighted genes such as MTOR, PLA2G7, MAPKAPK3, ANGPTL1, and ARNT as prospective therapeutic targets. The therapeutic potential of these candidate genes was validated with observations from existing drug trial databases. Our robust genetic and transcriptomic approach has identified promising directions for novel AMD interventions, emphasizing the significance of an integrated multiomic approach in tackling this important cause of visual impairment.

immunology↗

bioRxiv2024

Influences of single mutation and retinal binding on the THz absorption spectra of CRABP-II based rhodopsin mimics

The collective vibration of many biomolecules such as the skeleton vibration, dipole rotation and conformational bending falls in the terahertz (THz) frequency domain. Terahertz time-domain spectroscopy (THZ-TDS), which is very sensitive to the conformational changes, can be used to characterize the collective vibration of biomolecules. In this study, we investigated the low-frequency THz absorption spectra of two rhodopsin mimics using transmission THz-TDS. Using the normal model analysis (NMA), we successfully modelled the experimental terahertz absorption curve and attributed a unique collective motion pattern to each distinctive terahertz absorption frequency. By comparing the terahertz absorption spectra between without and with retinal, we show that the retinal binding can significantly alters the terahertz absorption spectra as well as the vibration modes. Furthermore, by comparing the terahertz absorption spectra between the two mutants, we observed that the single mutation can significantly change the influence of retinal binding on the terahertz absorption spectrum.

biophysics↗

bioRxiv2024

Nanocluster-antibody-drug conjugates (NADC) as an intravesical precision theranostic agent for interstitial cystitis

Interstitial cystitis (IC) is a chronic inflammatory bladder disorder with recurring severe pain, lacking timely diagnostic and therapeutic options. Here, we propose a unitary theranostic nanocluster-antibody-drug conjugate (NADC) by covalently placing dihydroorotate dehydrogenase inhibitors (DHODHi) and ultrasmall gold quantum clusters (AuQCs) on a nerve growth factor (NGF) antagonistic antibody with simultaneous X-ray computed tomographic and near-infrared fluorescence imaging contrasts. Combining anti-inflammatory effects from all individual components, intravesical NADC specifically homed to mucosal lesions with NGF overexpression in voided bladder and capably alleviated inflammation in chronic, acute, and prophylactic IC models of rats, as revealed by behavioral and pathological evaluations. Transcriptomics unveiled cytokine modulation and concomitant inhibition of perturbed IL-17, NF-{kappa}B, TNF, and JAK-STAT signaling pathways. Notably, NADC indirectly remodeled the host bladder microbiota by differentially varying anti-inflammatory and pro-inflammatory bacteria diversities. Distinct from conventional nanoparticles conjugated with antibodies and drugs, NADC relies on the antibody framework, outperforms clinical standard-of-care agents, and represents an emerging category of precision theranostic agents with translational potential for IC theranostics in clinical practice.

microbiology↗

bioRxiv2024

Cytosolic Ribosomal Protein Haploinsufficiency affects Mitochondrial Morphology and Respiration

The interplay between ribosomal protein composition and mitochondrial function is essential for sustaining energy homeostasis. Precise stoichiometric production of ribosomal proteins is crucial to maximize protein synthesis efficiency while reducing the energy costs to the cell. However, the impact of this balance on mitochondrial ATP generation, morphology and function remains unclear. Particularly, the loss of a single copy ribosomal protein gene is observed in Mendelian disorders like Diamond Blackfan Anemia and is common in somatic tumors, yet the implications of this imbalance on mitochondrial function and energy dynamics are still unclear. In this study, we investigated the impact of haploinsufficiency for four ribosomal protein genes implicated in ribosomopathy disorders (rps-10, rpl-5, rpl-33, rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells. Our findings uncover significant, albeit variably penetrant, mitochondrial morphological differences across these mutants, alongside an upregulation of glutathione transferases, and SKN-1 dependent increase in oxidative stress resistance, indicative of increased ROS production. Specifically, loss of a single copy of rps-10 in C. elegans led to decreased mitochondrial activity, characterized by lower energy levels and reduced oxygen consumption. A similar reduction in mitochondrial activity and energy levels was observed in human leukemia cells with a 50% reduction in RPS10 transcript levels. Importantly, we also observed alterations in the translation efficiency of nuclear and mitochondrial electron transport chain components in response to reductions in ribosomal protein genes expression in both C. elegans and human cells. This suggests a conserved mechanism whereby the synthesis of components vital for mitochondrial function are adjusted in the face of compromised ribosomal machinery. Finally, mitochondrial membrane and cytosolic ribosomal components exhibited significant covariation at the RNA and translation efficiency level in lymphoblastoid cells across a diverse group of individuals, emphasizing the interplay between the protein synthesis machinery and mitochondrial energy production. By uncovering the impact of ribosomal protein haploinsufficiency on the translation efficiency of electron transport chain components, mitochondrial physiology, and the adaptive stress responses, we provide evidence for an evolutionarily conserved strategy to safeguard cellular functionality under genetic stress.

genetics↗

bioRxiv2024

Intracranial neural representation of phenomenal and access consciousness in the human brain

After more than 30 years of extensive investigation, impressive progress has been made in identifying the neural correlates of consciousness (NCC). However, the functional role of spatiotemporally distinct consciousness-related neural activity in conscious perception is debated. Based on empirical EEG findings, e.g., of the enhanced early negative wave and late positive wave under conscious conditions, an influential framework proposed that consciousness-related neural activities could be dissociated into two distinct processes: phenomenal and access consciousness. This framework has been supported mainly by comparison of neural activity between report and no-report paradigms; however, though hotly debated, its authenticity has not been examined in a single paradigm with more informative intracranial recordings. In the present study, we employed a novel visual awareness task and recorded the local field potential (LFP) of epilepsy patients with electrodes implanted in cortical and subcortical regions. Overall, we found that the latency of visual awareness-related activity exhibited a bimodal distribution, and the recording sites with short and long latencies were largely separated in location, except in the lateral prefrontal cortex (lPFC). The mixture of short and long latencies in the lPFC indicates that it plays a critical role in linking phenomenal and access consciousness. However, the division between the two is not as simple as the central sulcus, as proposed previously. Moreover, in 4 patients with electrodes implanted in the bilateral prefrontal cortex, early awareness-related activity was confined to the contralateral side, while late awareness-related activity appeared on both sides. Finally, Granger causality analysis showed that awareness-related information flowed from the early sites to the late sites. These results provide the first LFP evidence of neural correlates of phenomenal and access consciousness, which sheds light on the spatiotemporal dynamics of NCC in the human brain.

neuroscience↗

bioRxiv2024

Human intralaminar and medial thalamic nuclei transiently gate conscious perception through the thalamocortical loop

Human high-order thalamic nuclei have been known to closely correlate with conscious states. However, given the great difference of conscious states and contents (conscious perception), it is nearly unknown how those thalamic nuclei and thalamocortical interactions directly contribute to the transient process of conscious perception. To address this question, we simultaneously recorded local field potentials (LFP) in the human intralaminar, medial and ventral thalamic nuclei as well as in the prefrontal cortex (PFC), while patients with implanted electrodes performing a visual consciousness task. Overall, compared to the ventral nuclei, intralaminar and medial nuclei showed earlier and stronger consciousness-related activity. Moreover, the transient thalamocortical neural synchrony and cross-frequency coupling were both driven by the theta phase of the intralaminar and medial nuclei during conscious perception. These results indicated that the intralaminar and medial thalamic nuclei, rather than the commonly believed PFC, play a decisive gate role in conscious perception. Highlights O_LIIntralaminar and medial thalamic nuclei showed earlier and stronger visual consciousness-related activity, comparing to the ventral nuclei. C_LIO_LIIntralaminar and medial thalamic transiently drove the thalamocortical synchronization through theta (2-8Hz) phase modulation during the emergence of visual consciousness. C_LIO_LITheta phase of intralaminar and medial thalamic activity dynamically regulated the amplitude of PFC activity during the emergence of consciousness. C_LIO_LIIntralaminar and medial thalamic nuclei showed more regulation on lateral PFC than on other PFC subregions during the emergence of consciousness. C_LI

neuroscience↗

bioRxiv2024

The origin and evolution of cultivated rice and genomic signatures of heterosis for yield traits in super-hybrid rice

Unraveling evolutionary history and genomic basis of heterosis is fundamental for advancing rice productivity. We developed a genome-scale phylogeny of Oryzeae by coalescing 39,984 gene trees. Our analysis supports parallel, independent origins and nearly synchronous evolutionary trajectories leading to the subsequent domestication of indica and japonica, evidenced by molecular dating and synonymous substitution rates for syntenic and domestication-associated genes. Our survey of 1,383 gene duplications in ancestor of O. sativa uncovers their roles in vital biological processes, highlighting the significance in environmental adaptability. Additionally, we confirm the lack of hybridization event among subspecies ancestors through gene tree topology and D-statistical analyses. We generated 71.67 GB whole-genome sequencing data for five super-hybrid rice varieties and their progenitors, revealing differential positive selection and genetic exchanges between subspecies, essential for heterosis formation. Crucially, our study underscores the role of non-additive gene expression in heterosis, particularly in genes associated with DNA repair and recombination, which may confer resistance traits. Furthermore, eQTL and de novo mutation analyses identify key developmental and stress response genes, offering targets for enhancing heterosis in rice. Overall, our research reveals crucial insights into the genetics of rice domestication and heterosis, offering a genomic resource to improve rices agricultural productivity.

evolutionary biology↗

bioRxiv2024

CD81+ fibroblasts, a unique subpopulation with accelerated cellular senescence, exaggerate inflammation and activate neutrophils via C3/C3aR1 axis in periodontitis

Periodontitis, a prevalent inflammatory disease worldwide, poses a significant economic burden on society and the country. Previous research has established a connection between cellular senescence and periodontitis. However, the role and mechanism of cell senescence in the progression of periodontitis have not been thoroughly investigated. This study aimed to explore the involvement of cellular senescence in the pathogenesis of periodontitis and determine the underlying mechanisms. Our findings demonstrated that senescent cells accumulated during the progress of periodontitis. Moreover, several scRNA-seq analysis suggested that gingival fibroblasts were the main cell population undergoing cellular senescence during periodontitis, which helps mitigate tissue damage and bone loss. Furthermore, we identified a high expression of CD81 in the senescent gingival fibroblast population. These cells were found to actively contribute to inflammation through their potent pro-inflammatory metabolic activity and secretion of SASP-related factors. Additionally, they recruited neutrophils via the C3/C3aR1 pathway, indirectly sustaining the inflammatory response. Senolytics via Navitoclax successfully alleviated inflammation and bone loss in periodontitis and administration of metformin could alleviate alleviated inflammation and bone loss in periodontitis through inhibiting cellular senescence. These results provide valuable insights into the cellular and molecular basis of periodontitis-induced tissue damage, highlighting the significance of fibroblast senescence. In conclusion, our study sheds light on the relationship between CD81 and cellular senescence, suggesting its potential as a therapeutic target for periodontitis.

immunology↗

bioRxiv2024

Dose-response functional and transcriptomic effects of follicle-stimulating hormone on ex vivo mouse folliculogenesis

The gonadotropin-dependent phase of ovarian folliculogenesis primarily requires follicle-stimulating hormone (FSH) to support one or multiple antral follicles, dependent on the species, to mature fully, enabling ovarian steroidogenesis, oogenesis, and ovulation to sustain female reproductive cycles and fertility. FSH binds to its membrane receptor in granulosa cells to activate various signal transduction pathways and gene regulatory networks. Poor female reproductive outcomes can result from both FSH insufficiency owing to genetic or non-genetic factors and FSH excess as encountered with ovarian stimulation in assisted reproductive technology (ART), but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and the threshold is moderately variable among individual follicles. FSH at subthreshold, threshold, and suprathreshold levels induced distinct expression patterns of follicle maturation-related genes and the follicular transcriptomics. The RNA-seq analysis identified novel genes and signaling pathways that may critically regulate follicle maturation. Suprathreshold FSH resulted in multiple ovarian disorders including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.

molecular biology↗

bioRxiv2024

Jianpi Jiedu Recipe inhibits proliferation through reactive oxygen species-induced incomplete autophagy and reduces PD-L1 expression in colon cancer

BackgroundJianpi Jiedu Recipe has been used to treat digestive tract tumors in China since ancient times, and its reliability has been proven by clinical research. Currently, the specific biological mechanism of JPJDR in treating tumors is unclear. MethodologyCCK-8 assay was used to detect cell viability. Clone formation assay and EdU assay were used to detect cell proliferation potential. DCFH-DA probe and JC-1 probe were used to detect total intracellular reactive oxygen species and mitochondrial membrane potential, respectively. Western blotting and immunofluorescence were used to detect protein expression level and subcellular localization of cells. RFP-GFP-LC3B reporter system was used to observe the type of autophagy in cells. Xenograft tumor model was used to study the therapeutic effect of JPJDR in vivo. ResultsJPJDR has a good inhibitory effect on various colorectal cancer cells and effectively reduces the proliferation ability of HT29 cells. After treatment with JPJDR, the amount of reactive oxygen species in HT29 cells increased significantly and the mitochondrial membrane potential decreased. JPJDR induced the accumulation of autophagosomes in HT29 cells and was shown to be incomplete autophagy. At the same time, JPJDR reduced the expression of PD-L1.Meanwhile, JPJDR can exert a good therapeutic effect in xenograft tumor mice. ConclusionJPJDR is a low-toxic and effective anti-tumor agent that can effectively treat colon cancer in vitro and in vivo. Its mechanism may be through inducing mitochondrial dysfunction and incomplete autophagy injury to inhibit the proliferation of colon cancer cells.

pharmacology and toxicology↗

bioRxiv2024

Causal mediation analysis for time-varying heritable risk factors with Mendelian Randomization

Understanding the causal mechanisms of diseases is crucial in clinical research. When randomized experiments are unavailable, Mendelian Randomization (MR) leverages genetic mutations to mitigate confounding. However, most MR analyses assume static risk factors, oversimplifying dynamic risk factor effects. The framework of life-course MR addresses this but struggles with limited GWAS cohort sizes and correlations across time points. We propose FLOW-MR, a computational approach estimating causal structural equations for temporally ordered traits using only GWAS summary statistics. FLOW-MR enables inference on direct, indirect, and path-wise causal effects, demonstrating superior efficiency and reliability, especially with noisy data. By incorporating a spike-and-slab prior, it mitigates challenges from extreme polygenicity and weak instruments. Applying FLOW-MR, we uncovered a childhood-specific protective effect of BMI on breast cancer and analyzed the evolving impacts of BMI, systolic blood pressure, and cholesterol on stroke risk, revealing their causal relationships.

genetics↗

bioRxiv2024

Enhancing Plant Photosynthesis using Carbon Dots as Light Converter and Photosensitizer

Improving photosynthetic efficiency is pivotal for CO2-based biomanufacturing and agriculture purposes. Despite the progress on photosynthetic biohybrids integrating biocatalysts with synthetic materials, nanomaterials with improved optical and photoelectrochemical properties are still needed to increase the energy-conversion efficiency. Here, we present a novel approach using carbon dots (CDs) as both intracellular photosensitizers and light converters for enhancing solar energy utilization in photosynthetic organisms. The CDs were produced from cyanobacterial biomass and used to convert a broad spectrum of solar irradiation to red light. We demonstrated that the nanosized CDs were incorporated into cyanobacterial cells and transferred light-excited electrons into the photosynthetic electron transfer chain. The biohybrids consisting of the CDs and Synechococcus elongatus exhibited increased growth rates, enhanced activities of both photosystems, and accelerated linear electron transport, compared with the cyanobacterial cells only. The supplementation of the CDs increased CO2-fixation rate and CO2-to-glycerol production by 2.4-fold and 2.2-fold, respectively. Furthermore, the CDs were shown to enhance photosynthesis and promote growth of Arabidopsis thaliana. The fresh weight of plant was increased 1.8-fold by CDs addition. These results reveal that simultaneous photosensitization and spectral modification could substantially improve the efficiency of natural photosynthesis. This study presents CDs as an attractive nanomaterial with great application potential in agriculture and solar-powered biomanufacturing.

synthetic biology↗

bioRxiv2024

Targeting resident astrocytes attenuates neuropathic pain after spinal cord injury

Astrocytes derive from different lineages and play a critical role in neuropathic pain after spinal cord injury (SCI). Whether selective eliminating these main origins of astrocytes in lumbar enlargement could attenuate SCI-induced neuropathic pain remains unclear. Through transgenic mice injected with an adeno-associated virus vector and diphtheria toxin, astrocytes in lumbar enlargement were lineage traced, targeted and selectively eliminated. Pain-related behaviors were measured with an electronic von Frey apparatus and a cold/hot plate after SCI. RNA sequencing, bioinformatics analysis, molecular experiment and immunohistochemistry were used to explore the potential mechanisms after astrocyte elimination. Lineage tracing revealed that the resident astrocytes but not ependymal cells were the main origins of astrocytes-induced neuropathic pain. SCI induced mice to obtain significant pain symptoms and astrocyte activation in lumbar enlargement. Selective resident astrocytes elimination in lumbar enlargement could attenuate neuropathic pain and activate microglia. Interestingly, the type I interferons (IFNs) signal was significantly activated after astrocytes elimination, and the most activated Gene Ontology terms and pathways were associated with the type I IFNs signal which was mainly activated in microglia and further verified in vitro and in vivo. Furthermore, different concentrations of interferon and Stimulator of interferon genes (STING) agonist could activate the type I IFNs signal in microglia. These results elucidate that selectively eliminating resident astrocytes attenuated neuropathic pain associated with type I IFNs signal activation in microglia. Targeting type I IFNs signal is proven to be an effective strategy for neuropathic pain treatment after SCI.

neuroscience↗

bioRxiv2024

Development of immobilized antibody-based affinity grid strategy and application in on-grid purification of target proteins for high-resolution cryo-EM

In cryo-electron microscopy (cryo-EM), sample preparation, especially for rare or fragile macromolecular assemblies and those suffering from air-water interface denaturation and particle orientation distribution problems, is a major bottleneck. Here, we developed and characterized an immobilized antibody-based affinity grid (IAAG) strategy based on the high-affinity PA tag/NZ-1 antibody epitope tag system. We used Pyr-NHS as a linker to immobilize NZ-1 Fab on the graphene oxide or carbon covered grid surface. We showed that the IAAG grid can enrich the PA-tagged target proteins, and overcome preferred orientation problems. Furthermore, we demonstrated that our IAAG strategy can be utilized for on-grid purification of low-abundance target complexes from cell lysates and enables atomic resolution cryo-EM. This approach greatly streamlines the purification process, reduces the need for large quantities of biological samples, and addresses common challenges encountered in cryo-EM sample preparation. Collectively, our IAAG strategy provides an efficient and robust means for combined sample purification and vitrification feasible for high-resolution cryo-EM. This approach also has the potential for broader applicability in cryo-EM and cryo-ET.

molecular biology↗

bioRxiv2023

Unbiased Complete Estimation of Chloroplast Number in Plant Cells Using Deep Learning Methods

Chloroplasts are essential organelles in plants that are involved in plant development and photosynthesis. Accurate quantification of chloroplast numbers is important for understanding the status and type of plant cells, as well as assessing photosynthetic potential and efficiency. Traditional methods of counting chloroplasts using microscopy are time-consuming and face challenges such as the possibility of missing out-of-focus samples or double counting when adjusting the focal position. Here, we developed an innovative approach called Detecting- and-Counting-chloroplasts (D&Cchl) for automated detection and counting of chloroplasts. This approach utilizes a deep-learning-based object detection algorithm called You-Only-Look-Once (YOLO), along with the Intersection Over Union (IOU) strategy. The application of D&Cchl has shown excellent performance in accurately identifying and quantifying chloroplasts. This holds true when applied to both a single image and a three-dimensional (3D) structure composed of a series of images. Furthermore, by integrating Cellpose, a cell-segmentation tool, we were able to successfully perform single-cell 3D chloroplast counting. Compared to manual counting methods, this approach improved the accuracy of detection and counting to over 95%. Together, our work not only provides an efficient and reliable tool for accurately analyzing the status of chloroplasts, enhancing our understanding of plant photosynthetic cells and growth characteristics, but also makes a significant contribution to the convergence of botany and deep learning. One-sentence summaryThis deep learning-based approach enables the accurate complete detection and counting of chloroplasts in 3D single cells using microscopic image stacks, and showcases a successful example of utilizing deep learning methods to analyze subcellular spatial information in plant cells. The authors responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (https://academic.oup.com/plcell/) is: Zhao Dong (dongzhao@hebeu.edu.cn), Shaokai Yang, (shaokai1@ualberta.ca), Ningjing Liu (liuningjing1@yeah.net), and Qiong Zhao (qzhao@bio.ecnu.edu.cn).

cell biology↗

bioRxiv2023

Liver Protects Cytoarchitecture, Neuron Viability and Electrocortical Activity in Post-Cardiac Arrest Brain Injury

BACKGROUNDBrain injury is the major reason for patient deaths in victims who survive after cardiac arrest. Clinical studies have shown that the presence of hypoxic hepatitis and pre-cardiac arrest liver disease is associated with increased mortality and inferior neurological recovery. However, how the liver might impact the pathogenesis of post-cardiac arrest is still unknown. METHODSAn in vivo global cerebral ischemia model was established to assess how simultaneous liver ischemia affected the recovery of brain ischemic injury. In addition, an ex vivo brain normothermic machine perfusion (NMP) model was established to evaluate how addition of a functioning liver might impact the circulation, cytoarchitecture, neuron viability and electrocortical activity of the reperfused brain post-cardiac arrest. RESULTSIn the in vivo model, we observed a larger infarct area in the frontal lobe, elevated tissue injury scores in the CA1 region, as well as increased intravascular immune cell adhesion in the reperfused brains with hepatic ischemia, compared to those without simultaneous hepatic ischemia. The results of the ex vivo model demonstrated that the addition of a functioning liver to the brain NMP circuit significantly reduced post-cardiac arrest brain injury, increased neuronal viability and improved electrocortical activity. Furthermore, we observed significant alterations in gene expressions and metabolites in the presence or absence of hepatic ischemia. CONCLUSIONSOur research highlights the crucial role of the liver in the pathogenesis of post-cardiac arrest brain injury. These findings shed lights on a cardio-pulmonary-hepatic brain resuscitation strategy for patients with cardiac arrest.

neuroscience↗

bioRxiv2023

Umbrella toxin particles produced by Streptomyces block mycelial growth of competing species

The Streptomyces are a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics derive. The production of these antibacterial molecules reflects the relentless competition Streptomyces engage in with other bacteria, including other Streptomyces species. Here we show that in addition to small molecule antibiotics, Streptomyces produce and secrete antibacterial protein complexes that feature a large, degenerate repeat-containing polymorphic toxin protein. A cryo-EM structure of these particles reveals an extended stalk topped by a ringed crown comprising the toxin repeats scaffolding five lectin-tipped spokes, leading to our naming them umbrella particles. S. coelicolor encodes three umbrella particles with distinct toxin and lectin composition, and supernatant containing these toxins specifically and potently inhibits the growth of select Streptomyces species from among a diverse collection of bacteria screened. For one target, S. griseus, we find inhibition relies on a single toxin and that intoxication manifests as rapid cessation of vegetative mycelial growth. Our data show that Streptomyces umbrella particles mediate competition between vegetative mycelia of related species, a function distinct from small molecule antibiotics, which are produced at the onset of reproductive growth and act broadly. Sequence analyses suggest this role of umbrella particles extends beyond Streptomyces, as we find umbrella loci in nearly one-thousand species across Actinobacteria.

microbiology↗

bioRxiv2023

Unveiling unique microbial nitrogen cycling and novel nitrification drivers in coastal Antarctica

Although microbial nitrogen (N) cycling plays a pivotal role in Antarctic ecosystems, its underlying mechanisms are largely uncharted. In this study, we unravel the biological origin of nitrate via triple oxygen isotopic composition analysis and systematically profile functional N-cycling genes within soil and lake sediment samples from the ice-free areas of East Antarctica. We successfully reconstruct 1,968 metagenome-assembled genomes (MAGs) spanning 29 microbial phyla, enabling the analysis of the presence or absence of 52 diverse metabolic marker genes. Consistent with quantitative data, our metagenomic analyses confirm the active processes of microbial nitrogen fixation, nitrification, and denitrification. We find no detectable anaerobic ammonium oxidation (anammox) processes, underscoring a unique microbial N-cycling dynamic in the region. Notably, we identify the predominance of complete ammonia-oxidizing (comammox) Nitrospira, a recently discovered bacterial guild capable of performing the entire nitrification process within a single organism. Further genomic investigations reveal their adaptive strategies in the Antarctic environment. These strategies likely involve the synthesis of trehalose to counteract cold stress, high substrate affinity to efficiently utilize available resources, and alternative metabolic pathways to adapt to nutrient-scarce conditions. Their significant role in the nitrification process is validated through 13C-DNA-based stable isotope probing (DNA-SIP). This research provides a comprehensive illustration of nitrifications crucial contribution to the nitrogen budget in coastal Antarctica, highlighting comammox Nitrospira clade B as a novel nitrifying agent and shedding new light on the complex biogeochemical processes of nitrogen cycling in coastal Antarctica.

microbiology↗