Biology subjects

Zeng, Q.

Publications and source records attributed to Zeng, Q..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Dynamic Modeling of Antibody Repertoire Reshaping in Response to Viral Infections

For many years, researchers have emphasized the production of high-affinity specific antibodies by hosts during viral infections. However, this has made it challenging for immunologists to systematically evaluate the initiation mechanisms of humoral immunity in specific immune responses. Employing mathematical modeling, we have systematically investigated the dynamic changes of the entire antibody atlas in response to exogenous antigenic stimuli, including viral infections. Our study reveals that the hosts antibody atlas is reshaped during viral infection, not through the proliferation of individual antibody types, but rather through the proliferation of antibody pools with strong binding activity. Moreover, we observe a contraction in pools of antibodies with low binding activity. We have identified the crucial role of self-antigens in maintaining antibody persistence, which can effectively explain the organisms lifelong protection against pathogens that are less prone to mutation. Using this model, we further explore the mechanisms underlying original antigenic sin and elucidate the specific practical applications of this model. This research transcends the limitations of mere mathematical parameter fitting, as we endeavor to elucidate the complex humoral immune processes using physical mechanisms as a foundation. Our work contributes to a renewed understanding of the antibody elicitation process in specific immune responses.

immunology↗

bioRxiv2024

Multiomics analyses decipher intricate changes in the cellular and metabolic landscape of steatotic livers upon dietary restriction and sleeve gastrectomy

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic, progressive liver disease that encompasses a spectrum of steatosis, steatohepatitis (or MASH), and fibrosis. Evidence suggests that dietary restriction (DR) and sleeve gastrectomy (SG) can lead to remission of hepatic steatosis and inflammation through weight loss, but it is unclear whether these procedures induce distinct metabolic or immunological changes in MASLD livers. This study aims to elucidate the intricate hepatic changes following DR, SG or sham surgery in rats fed a high-fat diet as a model of obesity-related MASLD, in comparison to a clinical cohort of patients undergoing SG. Single-cell and single-nuclei transcriptome analysis, spatial metabolomics, and immunohistochemistry revealed the liver landscape, while circulating biomarkers were measured in serum samples. Artificial intelligence (AI)-assisted image analysis characterized the spatial distribution of hepatocytes, myeloid cells and lymphocytes. In patients and experimental MASLD rats, SG improved BMI, circulating liver injury biomarkers and triglyceride levels. Both DR and SG attenuated liver steatosis and fibrosis in rats. Metabolism-related genes (Ppara, Cyp2e1 and Cyp7a1) were upregulated in hepatocytes upon DR and SG, while SG broadly upregulated lipid metabolism on cholangiocytes, monocytes, macrophages, and neutrophils. Furthermore, SG promoted myeloid cell accumulation in the liver not only ameliorating inflammation but activating liver repair processes. Regions with potent myeloid infiltration were marked with enhanced metabolic capacities upon SG. Additionally, a disruption of periportal hepatocyte functions was observed upon DR. In conclusion, this study indicates a dynamic cellular crosstalk in steatotic livers undergoing SG. Notably, PPAR- and gut-liver axis-related processes, and metabolically-active myeloid cell infiltration indicate intervention-related mechanisms supporting SG for the treatment of MASLD.

bioinformatics↗

bioRxiv2024

Single-nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root

Aortic root aneurysm is a potentially life-threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, our understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single-nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell-type-specific transcriptomic and cis-regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such as FOXN3, TEAD1, BACH2, and BACH1, are identified. In vitro experiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.

pathology↗

bioRxiv2024

Mathematical Modelling Indicates Th-cell Targeted Antibody-Dependent Cellular Cytotoxic Is a Crucial Obstacle Hurdling HIV Vaccine Development

HIV poses a significant threat to human health. Although some progress has been made in the development of an HIV vaccine, there is currently no reported success in achieving an effective and fully functional vaccine for HIV. This highlights the challenges involved in HIV vaccine development. Through mathematical modeling, we have conducted a systematic study on the impact of antibody-dependent cellular cytotoxicity (ADCC) on HIV-specific immune responses. Unlike other viral infections, the ADCC effect following HIV infection may cause significant damage to the follicular center Th cells, leading to apoptosis of follicular center cells and rapid death of effector Th cells. This impedes the generation of neutralizing antibodies and creates barriers to viral clearance, thereby contributing to long-term infection. Another challenge posed by this effect is the substantial reduction in vaccine effectiveness, as effective antigenic substances such as gp120 bind to Th cell surfaces, resulting in the apoptosis of follicular center Th cells due to ADCC, hindering antibody regeneration. To address this issue, we propose the concept of using bispecific antibodies. By genetically editing B cells to insert the bispecific antibody gene, which consists of two parts-one targeting the CD4 binding site of HIV, such as the broadly neutralizing antibody 3BNC117, and the other targeting antibodies against other viruses, such as the spike protein of SARS-CoV-2-we can simultaneously enhance the levels of two pathogen-specific antibodies through stimulation with non-HIV-antigens corresponding to the other part of the chimeric antibody, such as the spike protein. This study contributes to the elucidation of the pathophysiology of HIV, while also providing a theoretical framework for the successful development of an HIV vaccine.

immunology↗

bioRxiv2023

Aberrant methylation and expression of TNXB promotes chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N = 5) and osteoarthritis (N = 5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

molecular biology↗

bioRxiv2023

RankCompV3: a differential expression analysis algorithm based on relative expression orderings and applications in single-cell RNA transcriptomics

Effective identification of differentially expressed genes (DEGs) has been challenging for single-cell RNA sequencing (scRNA-seq) profiles. Many existing algorithms have high false positive rates (FPRs) and often fail to identify weak biological signals. Here, we present a novel method for identifying DEGs in scRNA-seq data called RankCompV3. It is based on the comparison of relative expression orderings (REOs) of gene pairs which are determined by comparing the expression levels of a pair of genes in a set of single-cell profiles. The numbers of genes with consistently higher or lower expression levels than the gene of interest are counted in two groups in comparison, respectively, and the result is tabulated in a 3x3 contingency table which is tested by McCullaghs method to determine if the gene is dysregulated. In both simulated and real scRNA-seq data, RankCompV3 tightly controlled the FPR and demonstrated high accuracy, outperforming 11 other common single-cell DEG detection algorithms. Analysis with either regular single-cell or synthetic pseudo-bulk profiles produced highly concordant DEGs with ground-truth. In addition, RankCompV3 demonstrates higher sensitivity to weak biological signals than other methods. The algorithm was implemented using Julia and can be called in R. The source code is available at https://github.com/pathint/RankCompV3.jl.

bioinformatics↗

bioRxiv2023

Diversity of Bathyarchaeia viruses in metagenomes and virus-encoded CRISPR system components

Bathyarchaeia represent a class of archaea common and abundant in sedimentary ecosystems. The virome of Bathyarchaeia so far has not been characterized. Here we report 56 metagenome-assembled genomes of Bathyarchaeia viruses identified in metagenomes from different environments. Gene sharing network and phylogenomic analyses led to the proposal of four virus families, including viruses of the realms Duplodnaviria and Adnaviria, and archaea-specific spindle-shaped viruses. Genomic analyses uncovered diverse CRISPR elements in these viruses. Viruses of the proposed family Fuxiviridae harbor an atypical type IV-B CRISPR-Cas system and a Cas4 protein that might interfere with host immunity. Viruses of the family Chiyouviridae encode a Cas2-like endonuclease and two mini-CRISPR arrays, one with a repeat identical to that in the host CRISPR array, potentially allowing the virus to recruit the host CRISPR adaptation machinery to acquire spacers that could contribute to competition with other mobile genetic elements or to inhibition of host defenses. These findings present an outline of the Bathyarchaeia virome and offer a glimpse into their counter-defense mechanisms.

microbiology↗

bioRxiv2023

Next-generation anti-PD-L1/IL-15 immunocytokine elicits superior antitumor immunity in cold tumors with minimal toxicity

Immunocytokines, such as anti-PD-L1/IL-15, have shown promising efficacy in preclinical studies, but their clinical development still faces severe safety concerns, with the problem not easily overcome by simply reducing the cytokine activity. We proposed a next-generation immunocytokine concept of designing a tumor-conditional anti-PD-L1/IL-15 prodrug (LH05), which innovatively masks IL-15 with steric hindrance of its flanking moieties of anti-PD-L1 and IL-15R-sushi domain. The design successfully attenuated the cytokine sink effect of IL-15 and resulted in a significantly reduced systemic toxicity when compared to wild-type anti-PD-L1/IL-15. LH05 would be specifically cleaved in the tumor microenvironment (TME) to release the active IL-15/IL-15R-sushi domain (ILR) in a proteolytic cleavage-dependent manner and exhibited potent antitumor effects in mouse syngeneic models. Mechanistically, the antitumor efficacy of LH05 was dependent on both innate and adaptive immunity, which altered the TME to Th1-type by recruiting and stimulating both NK and CD8+ T cells and fired up cold tumors. LH05 also showed superior efficacy in restoring immunotherapy response in a refractory U251 xenograft model. Collectively, we introduced a novel next-generation immunocytokine strategy for tumor immunotherapy, contributing to the establishment of optimal treatment for patients with resistance to immune checkpoint inhibitors or cold tumors.

bioengineering↗

bioRxiv2023

Using UAV-based temporal spectral indices to dissect changes in the stay green trait in wheat

Stay green (SG) in wheat, a beneficial trait for increasing yield and stress resistance, needs to be supported by analysis of the underlying genetic basis. Spectral reflectance indices (SIs) provide non-destructive tools to evaluate crop temporal senescence. However, few SI-based SG quantification pipelines for analyzing diverse wheat panels in the field are available. Here, we first applied SIs to monitor the senescence dynamics of 565 diverse wheat accessions from anthesis to maturation stages during two field seasons. Based on over 12,000 SIs data set, four SIs (NDVI, GNDVI, NDRE and OSAVI) were selected to develop relative stay green scores (RSGS) and the senescence of wheat populations occurs mainly at four developmental stages stage 1 (S1) to S4, accounting for the final SG indicators. A RSGS-based genome-wide association study identified 47 high-confidence quantitative trait loci (QTL) harboring 3,079 SNPs significantly associated with RSGS and 1,085 corresponding candidate genes in the two seasons; 15 QTL overlapped or were adjacent to known SG-related QTL or genes and the remaining QTL were novel. Finally, we selected three superior candidate genes (TraesCS6B03G0356400, TraesCS2B03G1299500, and TraesCS2A03G1081100) as examples by transcriptomes, gene annotation, and gene-based association analysis for further analysis and found that utilization of superior SG-related variation in China gradually increased following the Green Revolution. The study provides a useful reference for further SG-related gene discovery of favorable variations in diverse wheat panels.

genetics↗

bioRxiv2023

The TOR signaling pathway regulates vegetative development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus

The target of rapamycin (TOR) signaling pathway is highly conserved and plays a crucial role in diverse biological processes in eukaryotes. Despite its significance, the underlying mechanism of the TOR pathway in A. flavus remains elusive. In this study, we comprehensively analyzed the TOR signaling pathway in A. flavus by identifying and characterizing nine genes that encode distinct components of this pathway. The FK506-binding protein Fkbp3 and its lysine succinylation are important for aflatoxin production and rapamycin resistance. The TorA kinase plays a pivotal role in the regulation of growth, spore production, aflatoxin biosynthesis, and responses to rapamycin and cell membrane stress. As a significant downstream effector molecule of the TorA kinase, the Sch9 kinase regulates aflatoxin B1 (AFB1) synthesis, osmotic and calcium stress response in A. flavus, and this regulation is mediated through its S_TKc, S_TK_X domains, and the ATP binding site at K340. We also showed that the Sch9 kinase may have a regulatory impact on the high-osmolarity glycerol (HOG) signaling pathway. TapA and TipA, the other downstream components of the TorA kinase, play a significant role in regulating cell wall stress response in A. flavus. Moreover, the members of the TapA-phosphatase complexes, SitA and Ppg1, are important for various biological processes in A. flavus, including vegetative growth, sclerotia formation, AFB1 biosynthesis, and pathogenicity. We also demonstrated that SitA and Ppg1 are involved in regulating lipid droplets (LDs) biogenesis and cell wall integrity (CWI) signaling pathways. In addition, another phosphatase complex, Nem1/Spo7, plays critical roles in hyphal development, conidiation, aflatoxin production, and lipid droplets biogenesis. Collectively, our study has provided important insight into the regulatory network of the TOR signaling pathway and has elucidated the underlying molecular mechanisms of aflatoxin biosynthesis in A. flavus.

microbiology↗

bioRxiv2023

Whole genome sequencing reveals autooctoploidy in the Chinese sturgeon and its evolutionary trajectories

The Order Acipenseriformes, which include sturgeons and paddlefishes, represent "living fossils" with complex genomes that are good models for understanding whole genome duplication (WGD) and ploidy evolution in fishes. Here we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8 n), a hexavalent (6 n), two tetravalents (4 n), and a divalent (2 n). We propose based on an analysis taking into account delayed rediploidization that its octoploid genome composition results from two rounds of homologous whole genome duplications (WGDs), and further provide insight into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy composition and evolutionary trajectories of polyploidy fishes.

genomics↗

bioRxiv2023

Impact of inter-species interactions between flower microbiota commensals and a floral pathogen on disease incidence and pathogen activity

Flowers are colonized by a diverse community of microorganisms that alter plant health and interact with floral pathogens. Erwinia amylovora is a flower-inhabiting bacterium and a pathogen that infects different plant species, including Malus x domestica (apple). Previously, we showed that the co-inoculation of two bacterial strains, Pseudomonas and Pantoea natural inhabitants of apple flowers, reduced disease incidence caused by this floral pathogen. Here, we decipher the ecological interactions between these two flower-associated bacteria and E. amylovora in field experimentation and in vitro co-cultures. The two flower microbiota strains did not competitively exclude E. amylovora from the stigma habitat, as both commensal bacteria and the pathogen co-existed on the apple flowers, proscribing microbial antibiosis or niche exclusion as predominant mechanisms of host protection. Inspection of the total and the active microbiota populations on flowers revealed that strain co-inoculations altered microbiota activity. Using synthetic stigma exudation medium, tripartite co-culture of the bacterial strains strongly acidified the growth milieu and led to a substantial alteration of gene expression in both the pathogen and the two microbiota members. Our study emphasizes the critical role of emergent properties mediated by inter-species interactions within the plant holobiont and their impact on plant health and pathogen behavior. ImportanceFire blight, caused by Erwinia amylovora, is one of the most important plant diseases of pome fruits. Plant-associated microbiota can influence plant disease occurrence through inter-species interactions. Previous studies have shown that plant microbiota commensals could suppress disease mainly by antagonizing of the pathogen growth, however, whether plant-associated microbiota could alter pathogen activity and behavior have not been well studied. Here, we show that the co-inoculation of two bacterial strains that naturally colonize the apple flowers reduce disease pressure. We further demonstrate that the interactions between these two microbiota commensals and the floral pathogen lead to a strong alteration of the pH and to the emergence of new gene expression patterns that may alter the pathogen behavior. Our findings emphasize the critical role of emergent properties mediated by inter-species interactions between plant microbiota and plant pathogens and their impact on plant health.

microbiology↗

bioRxiv2023

Genetic basis of expression and splicing underlying spike architecture in wheat (Triticum aestivum L.)

IntroductionWheat is one of the most important staple crops worldwide, and an important source of human protein and mineral element intake. Continuously increasing stable production of wheat is critical for global food security under the challenge of population growth and limited resource input. ObjectiveSpike architecture determines the potential grain yield of wheat. However, the mechanisms of transcriptional regulation of spike architecture in wheat remain largely unknown, limiting further genetic improvement of wheat yield. In this study we explored the genetic basis of spike architecture in wheat. MethodsPopulation RNA-seq methods were used to identify the eQTLs and sQTLs associated with spike architecture and applied this to dissection of the genetic basis of gene expression and splicing controlling these complex yield-related traits. ResultsIn total, 4,143 expression quantitative trait loci (eQTLs) and 12,933 splice QTLs (sQTLs) were identified in wheat based on 178 RNA-seq samples, revealing 774 cis-eQTLs and 321 cis-sQTLs for 86 eGenes and 73 sGenes, respectively. Integration of eQTLs and sQTLs with genome-wide association study (GWAS) identified dozens of additional novel candidate genes that may contribute to spike-related traits. Gene network analysis showed that eQTLs and sQTLs were widely involved in the co-expression modules that regulate wheat spike architecture. Notably, the eQTL locus AX-108754757 regulated the expression of 5 eGenes that negatively controled grain number per spike. AX-111592099 regulated both the splicing and expression of TraesCS7B02G442100, encoding an E3 ubiquitin ligase, and playing a central role in regulating spike length. ConclusionThis study provides new insights into the genetic basis of spike architecture. This improved understanding of spike-related traits in wheat will contribute to more rapid genetic improvement.

plant biology↗

bioRxiv2023

Brain-wide Correspondence Between Neuronal Epigenomics and Long-Distance Projections

Single-cell genetic and epigenetic analyses parse the brains billions of neurons into thousands of "cell-type" clusters, each residing in different brain structures. Many of these cell types mediate their unique functions by virtue of targeted long-distance axonal projections to allow interactions between specific cell types. Here we have used Epi-Retro-Seq to link single cell epigenomes and associated cell types to their long-distance projections for 33,034 neurons dissected from 32 different source regions projecting to 24 different targets (225 source [->]target combinations) across the whole mouse brain. We highlight uses of this large data set for interrogating both overarching principles relating projection cell types to their transcriptomic and epigenomic properties and for addressing and developing specific hypotheses about cell types and connections as they relate to genetics. We provide an overall synthesis of the data set with 926 statistical comparisons of the discriminability of neurons projecting to each target for every dissected source region. We integrate this dataset into the larger, annotated BICCN cell type atlas composed of millions of neurons to link projection cell types to consensus clusters. Integration with spatial transcriptomic data further assigns projection-enriched clusters to much smaller source regions than afforded by the original dissections. We exemplify these capabilities by presenting in-depth analyses of neurons with identified projections from the hypothalamus, thalamus, hindbrain, amygdala, and midbrain to provide new insights into the properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription factor binding motifs, and neurotransmitter usage.

neuroscience↗

bioRxiv2023

Single-cell DNA Methylome and 3D Multi-omic Atlas of the Adult Mouse Brain

Cytosine DNA methylation is essential in brain development and has been implicated in various neurological disorders. A comprehensive understanding of DNA methylation diversity across the entire brain in the context of the brains 3D spatial organization is essential for building a complete molecular atlas of brain cell types and understanding their gene regulatory landscapes. To this end, we employed optimized single-nucleus methylome (snmC-seq3) and multi-omic (snm3C-seq1) sequencing technologies to generate 301,626 methylomes and 176,003 chromatin conformation/methylome joint profiles from 117 dissected regions throughout the adult mouse brain. Using iterative clustering and integrating with companion whole-brain transcriptome and chromatin accessibility datasets, we constructed a methylation-based cell type taxonomy that contains 4,673 cell groups and 261 cross-modality-annotated subclasses. We identified millions of differentially methylated regions (DMRs) across the genome, representing potential gene regulation elements. Notably, we observed spatial cytosine methylation patterns on both genes and regulatory elements in cell types within and across brain regions. Brain-wide multiplexed error-robust fluorescence in situ hybridization (MERFISH2) data validated the association of this spatial epigenetic diversity with transcription and allowed the mapping of the DNA methylation and topology information into anatomical structures more precisely than our dissections. Furthermore, multi-scale chromatin conformation diversities occur in important neuronal genes, highly associated with DNA methylation and transcription changes. Brain-wide cell type comparison allowed us to build a regulatory model for each gene, linking transcription factors, DMRs, chromatin contacts, and downstream genes to establish regulatory networks. Finally, intragenic DNA methylation and chromatin conformation patterns predicted alternative gene isoform expression observed in a companion whole-brain SMART-seq3 dataset. Our study establishes the first brain-wide, single-cell resolution DNA methylome and 3D multi-omic atlas, providing an unparalleled resource for comprehending the mouse brains cellular-spatial and regulatory genome diversity.

genomics↗

bioRxiv2023

Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease

Somatic mutations in non-malignant tissues accumulate with age and insult, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate mutations found in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to non-alcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7, a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance. Next, we induced pooled mosaicism in 63 known NASH genes, allowing us to trace mutant clones side-by-side. This in vivo tracing platform, which we coined MOSAICS, selected for mutations that ameliorate lipotoxicity, including mutant genes identified in human NASH. To prioritize new genes, additional screening of 472 candidates identified 23 somatic perturbations that promoted clonal expansion. In validation studies, liver-wide deletion of Bcl6, Tbx3, or Smyd2 resulted in protection against NASH. Selection for clonal fitness in mouse and human livers identifies pathways that regulate metabolic disease. HighlightsO_LIMosaic Mboat7 mutations that increase lipotoxicity lead to clonal disappearance in NASH. C_LIO_LIIn vivo screening can identify genes that alter hepatocyte fitness in NASH. C_LIO_LIMosaic Gpam mutations are positively selected due to reduced lipogenesis. C_LIO_LIIn vivo screening of transcription factors and epifactors identified new therapeutic targets in NASH. C_LI

cell biology↗

bioRxiv2023

Modification of social cheating facilitates the stabilization and chronic infection of polymorphic Pseudomonas aeruginosa population

Chronic infection of the common bacterial pathogen Pseudomonas aeruginosa frequently leads to the coexistence of heterogeneous individuals to engage in several group behaviors. However, further evolution of the polymorphic P. aeruginosa population, including the dynamic change of social cooperation and its impact on host immune system, still remain elusive. We show that the evolution of P. aeruginosa in the patients with chronic obstructive pulmonary disease frequently selects the isolates deficient in producing the costly and sharable extracellular products for nutrient acquisition. The evolution of polymorphic P. aeruginosa population is mainly concentrated on modifying the adaptability of lasR mutants, which are typical cheaters in the competition of quorum-sensing-controlled extracellular proteases. Importantly, lasR mutants with varying degrees of evolution interact with wild-type P. aeruginosa in a framework termed cascaded public goods game to compete for extracellular proteases and siderophores, and thus perpetuate social cooperation under different conditions. Finally, we find that a polymorphic population comprised of lasR-intact P. aeruginosa and evolved lasR-mutant can minimize the host immune fluctuation for persistent colonization. This study demonstrates the multistage evolution and complex interaction of P. aeruginosa in adaptation to host lungs, and provides an explanation for the success of cooperation in public goods game.

microbiology↗

bioRxiv2023

Dominant Role of Stochastic Processes in Soil Fungal Communities in Pioneer Forests at a Regional Scale

Soil fungal community assembly is driven by deterministic and stochastic processes. However, the contribution of these mechanisms to structure the composition of fungal communities of forest soils at the regional scale is poorly known. Here, we investigate the relative importance of deterministic and stochastic processes on fungal community composition by rDNA ITS metabarcoding in a Populus davidiana pioneer forests along spatial-temporal gradients. We also assessed the impact of elevation and seasonality. The soil fungal richness of P. davidiana pioneer forests was significantly affected by elevation and less affected by season. Similarly, the variation in the fungal community composition according to the elevation was greater than the effect of seasonality. The fungal community composition showed a significant distance-decay relationship. Variation partitioning analysis showed that plant variables explained the soil fungal community variation. Through null model analysis, we found that stochastic processes were dominant in the soil fungal community assembly. However, the relative importance of ecological processes, including dispersal, selection, and drift, was not consistent across the four soil fungal community assemblies. In addition, the undominated fraction (including weak selection, weak dispersal, diversification and drift) had a high relative contribution to the soil fungal community assembly process in the P. davidiana pioneer forest. In summary, our results demonstrated that plant variables and the undominated fraction dominate the deterministic and stochastic processes driving soil fungal community assemblies in a P. davidiana pioneer forest at the regional scale, which provides new perspectives for the regional scale studies of soil fungi. IMPORTANCEElevation and seasonality are important factors driving the composition of soil microbiota. Due to the tight interactions of soil fungi with their host trees in forest ecosystems, the spatial variation of soil fungal community is often linked to the variation in the composition of dominant tree species. We compared the responses of soil fungal communities to seasonal and spatial changes at four levels in a temperate poplar forest dominated by a single tree species under elevation changes. Elevation had a higher impact than seasonality on the soil fungal beta diversity. Even when the shift in dominant tree species was limited, vegetation factors still impact soil fungal community variations. The dominant role of homogeneous selection and drift in fungal community assemblies, except for ectomycorrhizal fungi, was further discovered.

microbiology↗