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High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co- infections by other pathogens and their involvement in the severity of COVID-19.

IntroductionCitrus is one of the most important fruit crops worldwide, and the root-associated microbiota can have a profound impact on tree health and growth.MethodsIn a collaborative effort, the International Citrus Microbiome Consortium investigated the global citrus root microbiota with samples collected from nine citrus-producing countries across six continents. We analyzed 16S rDNA and ITS2 amplicon sequencing data to identify predominant prokaryotic and fungal taxa in citrus root samples. Comparative analyses were conducted between root-associated microbial communities and those from the corresponding rhizosphere and bulk soil samples. Additionally, genotype-based group-wise comparisons were performed to assess the impact of citrus genotype on root microbiota composition.ResultsTen predominant prokaryotic phyla, containing nine bacterial phyla including Proteobacteria, Actinobacteria, Acidobacteria, and Bacteroidetes and one archaeal phylum (Thaumarchaeota), and multiple fungal phyla including Ascomycota and Basidiomycota were identified in the citrus root samples. Compared with the microbial communities from the corresponding rhizosphere and bulk soil samples from the same trees, the prokaryotic and fungal communities in the roots exhibited lower diversity and complexity but greater modularity compared to those in the rhizosphere. In total, 30 root-enriched and 150 root-depleted genera in bacterial community were identified, whereas 21 fungal genera were enriched, and 147 fungal genera were depleted in the root niche compared with the rhizosphere. The citrus genotype significantly affected the root prokaryotic and fungal communities. In addition, we have identified the core root prokaryotic genera comprising Acidibacter, Allorhizobium, Bradyrhizobium, Chitinophaga, Cupriavidus, Devosia, Dongia, Niastella, Pseudomonas, Sphingobium, Steroidobacter and Streptomyces, and the core fungal genera including Acrocalymma, Cladosporium, Fusarium, Gibberella, Mortierella, Neocosmospora and Volutella. The potential functions of these core genera of root microbiota were predicted.ConclusionOverall, this study provides new insights into the assembly of microbial communities and identifies core members of citrus root microbiota across a wide geographic range. The findings offer valuable information for manipulating root microbiota to enhance plant growth and health.

Abstract Greenspaces are important for sustaining healthy urban environments and their human populations. Yet their capacity to support multiple ecosystem services simultaneously (multiservices) compared with nearby natural ecosystems remains virtually unknown. We conducted a global field survey in 56 urban areas to investigate the influence of urban greenspaces on 23 soil and plant attributes and compared them with nearby natural environments. We show that, in general, urban greenspaces and nearby natural areas support similar levels of soil multiservices, with only six of 23 attributes (available phosphorus, water holding capacity, water respiration, plant cover, arbuscular mycorrhizal fungi (AMF), and arachnid richness) significantly greater in greenspaces, and one (available ammonium) greater in natural areas. Further analyses showed that, although natural areas and urban greenspaces delivered a similar number of services at low (>25% threshold) and moderate (>50%) levels of functioning, natural systems supported significantly more functions at high (>75%) levels of functioning. Management practices (mowing) played an important role in explaining urban ecosystem services, but there were no effects of fertilisation or irrigation. Some services declined with increasing site size, for both greenspaces and natural areas. Our work highlights the fact that urban greenspaces are more similar to natural environments than previously reported and underscores the importance of managing urban greenspaces not only for their social and recreational values, but for supporting multiple ecosystem services on which soils and human well-being depends.

Abstract Introduction The application of host‐derived antibacterial peptides has been highlighted as a potential efficacious and safe tool for the treatment of Huanglongbing (HLB), the most devastating disease of citrus. However, pathogenic bacteria such as HLB‐causing Candidatus liberibacter asiaticus (CLas) often develop resistance against the host antibacterial peptides. We showed that chimeras containing two different host antibacterial peptides not only retain antibacterial activity but also overcome bacterial resistance and enhance plant defence responses. Also, chimeric peptides can have an off‐target impact on the structure and function of plant‐associated microbiomes. However, there is a lack of understanding of the impact of the chimeric peptide therapy on the microbial structure in the citrus phyllosphere while reducing the CLas titre. Here, we aim to evaluate the efficacy of a chimeric peptide (UGK17) to reduce CLas titre, inducing plant defence response and impacting the microbiome associated with the citrus phyllosphere. Material and Method Leaf samples were collected from orange and grapefruit trees in Texas and identified as old and young leaves according to their maturity. We collected three different types of leaves based on their infection and symptoms: healthy, symptomatic (infected with typical symptoms), and asymptomatic (infected without symptoms). In planta assay was performed by dipping the leaves in the 0, 5 and 25 μM of UGK17 solutions for 48 h. The quantifications of CLas titre and pathogenesis‐related (PR) gene expression were done by quantitative polymerase chain reaction (qPCR) and reverse transcription‐qPCR, respectively. Amplicon sequencing was done to evaluate the impact of UGK17 on individual bacterial community structures. In addition, we performed an ex planta assay to assess the effect of UGK17 on the growth of bacterial isolates including Liberibacter crescens instead of unculturable CLas predominant in the phyllosphere. Result The UGK17 treatment reduced the CLas titre in both asymptomatic and symptomatic citrus leaves, regardless of the age of the leaves. The UGK17 application augmented the PR gene expression. In ex planta assay, the growth of L. crescens along with four other strains belonging to the family Rhizobiaceae, was significantly inhibited by the UGK17 while the growth of 74 strains were unaffected. Additionally, there was no statistically significant changes in the microbial community structure with UGK17 treatment. Conclusion Our results suggest that the chimeric peptide therapy is a promising solution to combat HLB by targeting mainly Gram‐negative pathogens and enhancing the plant immune responses without impairing the indigenous microbial community in the citrus phyllosphere.

For a long time, microbial applications in crop production focused primarily on the symbiosis between mycorrhizal fungi and plants and the relationship between N2-fixing rhizobia and legumes. However, plant-associated microorganisms and microbiomes in general have lately gained immense attention, and the available information on the ecology and functions of microbiomes in the soil and plant environment exploded in the last decade. With this understanding, researchers as well as the industry have realized the vast potential of microorganisms to be used in agriculture and most importantly, to make farming more sustainable. Microorganisms have been shown to be applicable for plant protection and to improve plant nutrition. As a consequence, microbiome management can help to replace agrochemicals and increase environmental and human health. Furthermore, agriculture is facing various challenges related to climate change such as drought or emerging pathogens. Also, for these scenarios, microorganisms may find application to alleviate various abiotic and biotic stresses. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

BackgroundEBV infection has long been postulated to trigger multiple sclerosis (MS) and anti-EBV antibodies showed a consistent presence in MS patients. Previous reports from our group have shown that the EBV infects different brain cells. Entry of the virus in neuronal cells is assisted by several host factors including membrane cholesterol. By using an inhibitor, methyl-β-cyclodextrin (MβCD), we evaluated the role of membrane cholesterol in EBV infection and pathogenesisMethodologyThe membrane cholesterol depleted cells were infected with EBV and its latent genes expression were assessed. Further, EBV-mediated downstream signalling molecules namely STAT3, RIP, NF-kB and TNF-α levels was checked at protein level along with spatial (periphery and nucleus) and temporal changes in biomolecular fingerprints with Raman microspectroscopy (RS).ResultsUpon treatment with MβCD, lmp1 and lmp2a suggested significant downregulation compared to EBV infection. Downstream molecules like STAT3 and RIP, exhibited a decrease in protein levels temporally upon exposure to MβCD while NF-kB levels were found to be increased. Further, the intensity of the Raman spectra exhibited an increase in triglycerides and fatty acids in the cytoplasm of EBV-infected LN-229 cells compared to MβCD+EBV. Likewise, the Raman peak width of cholesterol, lipid and fatty acids were found to be reduced in EBV-infected samples indicates elevation in the cholesterol specific moieties. In contrast, an opposite pattern was observed in the nucleus. Moreover, the ingenuity pathway analysis revealed protein molecules such as VLDLR, MBP and APP that are associated with altered profile of cholesterol, fatty acids and triglycerides with infection-related CNS disorders.ConclusionTaken together, our results underline the important role of membrane cholesterol over EBV entry/pathogenesis in astroglia cells which further trigger/exacerbate virus-associated neuropathologies. These results likely to aid into the prognosis of neurological disease like MS.

Abstract Soil contamination is one of the main threats to ecosystem health and sustainability. Yet little is known about the extent to which soil contaminants differ between urban greenspaces and natural ecosystems. Here we show that urban greenspaces and adjacent natural areas (i.e., natural/semi-natural ecosystems) shared similar levels of multiple soil contaminants (metal(loid)s, pesticides, microplastics, and antibiotic resistance genes) across the globe. We reveal that human influence explained many forms of soil contamination worldwide. Socio-economic factors were integral to explaining the occurrence of soil contaminants worldwide. We further show that increased levels of multiple soil contaminants were linked with changes in microbial traits including genes associated with environmental stress resistance, nutrient cycling, and pathogenesis. Taken together, our work demonstrates that human-driven soil contamination in nearby natural areas mirrors that in urban greenspaces globally, and highlights that soil contaminants have the potential to cause dire consequences for ecosystem sustainability and human wellbeing.

Abstract Morphogenesis and organogenesis in the low organisms have been found to be modulated by a number of proteins, and one of such factor, deformed epidermal auto-regulatory factor-1 (DEAF-1) has been initially identified in Drosophila. The mammalian homologue of DEAF-1 and structurally related proteins have been identified, and they formed a family with over 20 members. The factors regulate gene expression through association with co-repressors, recognition of genomic marker, to exert histone modification by catalyze addition of some chemical groups to certain amino acid residues on histone and non-histone proteins, and degradation host proteins, so as to regulate cell cycle progression and execution of cell death. The formation of fused genes during chromosomal translocation, exemplified with myeloid transforming gene on chromosome 8 (MTG8)/eight-to-twenty one translocation (ETO) /ZMYND2, MTG receptor 1 (MTGR1)/ZMYND3, MTG on chromosome 16/MTGR2/ZMYND4 and BS69/ZMYND11 contributes to malignant transformation. Other anomaly like copy number variation (CNV) of BS69/ZMYND11 and promoter hyper methylation of BLU/ZMYND10 has been noted in malignancies. It has been reported that when fusing with Runt-related transcription factor 1 (RUNX1), the binding of MTG8/ZMYND2 with co-repressors is disturbed, and silencing of BLU/ZMYND10 abrogates its ability to inhibition of cell cycle and promotion of apoptotic death. Further characterization of the implication of ZMYND proteins in carcinogenesis would enhance understanding of the mechanisms of occurrence and early diagnosis of tumors, and effective antitumor efficacy.

Abstract Background Little is known about the global distribution and environmental drivers of key microbial functional traits such as antibiotic resistance genes (ARGs). Soils are one of Earth’s largest reservoirs of ARGs, which are integral for soil microbial competition, and have potential implications for plant and human health. Yet, their diversity and global patterns remain poorly described. Here, we analyzed 285 ARGs in soils from 1012 sites across all continents and created the first global atlas with the distributions of topsoil ARGs. Results We show that ARGs peaked in high latitude cold and boreal forests. Climatic seasonality and mobile genetic elements, associated with the transmission of antibiotic resistance, were also key drivers of their global distribution. Dominant ARGs were mainly related to multidrug resistance genes and efflux pump machineries. We further pinpointed the global hotspots of the diversity and proportions of soil ARGs. Conclusions Together, our work provides the foundation for a better understanding of the ecology and global distribution of the environmental soil antibiotic resistome. Video Abstract

Abstract Introduction Citrus greening (aka Huanglongbing, HLB) caused primarily by the bacterial pathogen Candidatus Liberibacter asiaticus (CLas) has devastating effects on the global citrus industry. Agricultural management‐induced changes in microbial communities are hypothesised to contribute toward HLB resistance by reducing pathogen titre and increasing root and soil health. However, we have a limited understanding of the impacts of management practices on the soil microbiome, making the extent of HLB management uncertain. Material and Methods Here we investigated the effect of agricultural management practices on reducing CLas titer via changes in rhizosphere‐associated bacterial communities. Rhizosphere and root samples were collected from two sites in Florida where different management practices (e.g., metalized reflective mulch ground covers, compost application and microbial inoculations) are currently being implemented to prevent HLB. Management‐induced changes in the rhizosphere bacterial community were assessed using amplicon sequencing. qPCR assays were used to quantify the titer of the pathogen CLas in roots. In addition, we measured soil properties and the activities of microbial enzymes involved in soil nutrient cycling. Results Our results indicated that certain management practices lead to shifts in the community structure of rhizosphere bacterial communities that negatively interact with the HLB pathogen. Management practices improved soil quality and reduced CLas titer. Additionally, we found that Actinobacteria were frequently enriched in the successful treatment sites, suggesting that Actinobacteria taxa could be indicators for HLB suppression properties in the soil. Conclusion Our results suggest that microbiome manipulation, either through changes in the management practices or microbial amendment, can increase the suppressive potential of soils, resulting in the reduction in CLas titer and potentially leading to HLB suppression in citrus groves.

Considering our growing population and our continuous degradation of soil environments, understanding the fundamental ecology of soil biota and plant microbiomes will be imperative to sustaining soil systems. Arbuscular mycorrhizal (AM) fungi extend their hyphae beyond plant root zones, creating microhabitats with bacterial symbionts for nutrient acquisition through a tripartite symbiotic relationship along with plants. Nonetheless, it is unclear what drives these AM fungal-bacterial relationships and how AM fungal functional traits contribute to these relationships. By delving into the literature, we look at the drivers and complexity behind AM fungal-bacterial relationships, describe the shift needed in AM fungal research towards the inclusion of interdisciplinary tools, and discuss the utilization of bacterial datasets to provide contextual evidence behind these complex relationships, bringing insights and new hypotheses to AM fungal functional traits. From this synthesis, we gather that interdependent microbial relationships are at the foundation of understanding microbiome functionality and deciphering microbial functional traits. We suggest using pattern-based inference tools along with machine learning to elucidate AM fungal-bacterial relationship trends, along with the utilization of synthetic communities, functional gene analyses, and metabolomics to understand how AM fungal and bacterial communities facilitate communication for the survival of host plant communities. These suggestions could result in improving microbial inocula and products, as well as a better understanding of complex relationships in terrestrial ecosystems that contribute to plant-soil feedbacks.

Soil health is an important aspect for maintaining adequate crop production, but the specifics of what entails a healthy soil can vary from region to region and crop to crop. In highly managed agricultural systems, unhealthy soil can be masked by intensive management practices, yet there must be detrimental cutoff points in various characteristics, such as soil organic matter (SOM) concentrations, where even highly managed systems start to lose productivity. This negative impact was observed in a Florida citrus grove containing Valencia orange trees with observable differences in tree size yet were otherwise managed identically. A soil health index demonstrated that the areas with smaller trees had a significantly lower index score and those soils contained significantly less SOM (average SOM ​= ​0.57%) compared to areas with larger trees (average SOM ​= ​0.94%). The areas of lower crop productivity also had less enzymatic activity of common carbon-cycling enzymes and different microbial populations, which all together negatively affected soil health and corresponding plant productivity. This agricultural region is also known to have a Citrus Greening disease (HLB) infection rate of close to 100%, hence we developed a hypothesis that could explain how progression of this infection could be impacted by SOM concentrations and differences in microbial diversity. We posit that areas of this grove with healthier soil could have more resistance to the onset of fatal HLB symptoms. Consequently, soil organic matter distribution and concentration should be considered when establishing new groves in order to optimize soil and crop productivity.

Abstract The soil microbiome response to global change drivers remains largely unclassified, with current studies showing contrasting results to several global change drivers. One such driver, drought, is increasing in severity and frequency due to climate change. Further, legacy effects, or long‐lasting impacts after drought has subsided, could have lasting impacts on the soil microbiome with important consequences for ecosystem functioning. Thus, our study aimed to understand how the soil microbiome responds after a severe, prolonged drought and whether legacy effects persist post‐drought. We measured soil microbial community response in a mesic grassland for two years after a four‐year experimental drought in a native tallgrass prairie. The experimental drought was imposed either (1) chronically by reducing each growing season rainfall event by 66% or (2) intensely by completely eliminating growing season rainfall until an ~45% reduction in mean annual rainfall (climatic average) was achieved. The bacterial community showed no legacies in the first season post‐drought in response to either chronic or intense drought but showed an increased abundance of Verrucomicrobia and decreased richness in both treatments in the second growing season after the drought treatments ended. In the first and second post‐drought growing seasons, we found small differences in beta diversity between the control and intense drought treatment for fungal communities but not for the chronic drought treatment. Further, we found that the two main phyla of fungi, Ascomycota and Basidiomycota, showed reduced relative abundance post‐drought in the intense drought treatment. Overall, few legacies in soil microbial communities persisted after a four‐year experimentally induced drought. However, our results show that the nature of the drought—chronic versus intense—can differentially impact fungal versus bacterial short‐term legacies. These results suggest that the soil microbiome is for the most part drought resistant (responds little during drought) and/or resilient (quickly recovers post‐drought, since a study at the same site found that drought impacted the bacterial community) in this mesic grassland.

Abstract Introduction Harnessing synthetic communities (SynCom) of plant growth‐promoting (PGP) microorganisms is considered a promising approach to improve crop fitness and productivity. However, biotic mechanisms that underpin improved plant performance and the effects of delivery mode of synthetic community are poorly understood. These are critical knowledge gaps that constrain field efficacy of SynCom and hence large‐scale adoption by the farming community. Material & Methods In this study, a SynCom of four PGP microbial species was constructed and applied to either as seed dressing (treatment T1, applied at the time of sowing) or to soil (treatment T2, applied in soil at true leaf stage) across five different cotton (Gossypium hirsutum) cultivars. The impact of SynCom on plant growth, rhizosphere microbiome and soil nutrient availability, and how this was modified by plant variety and mode of applications, was assessed. Results Results showed that the seed application of SynCom had the strongest positive impact on overall plant fitness, resulting in higher germination (14.3%), increased plant height (7.4%) and shoot biomass (5.4%). A significant increase in the number of flowers (10.4%) and yield (8.5%) was also observed in T1. The soil nitrate availability was enhanced by 28% and 55% under T1 and T2, respectively. Results further suggested that SynCom applications triggered enrichment of members from bacterial phyla Actinobacteria, Firmicutes and Cyanobacteria in the rhizosphere. A shift in fungal communities was also observed, with a significant increase in the relative abundance of fungi from phyla Chytridiomycota and Basidiomycota in SynCom treatments. A structural equation model suggested that SynCom directly increased crop productivity but also indirectly via impacting the alpha diversity of bacteria. Conclusion Overall, this study provides mechanistic evidence that SynCom applications can shift rhizosphere microbial communities and improve soil fertility, plant growth, and crop productivity, suggesting that their use could contribute toward sustainable increase in farm productivity.

Individual microbes often have defined relationships with their hosts that include beneficial, commensal, and pathogenic interactions. However, at the community level, plant microbiomes are considered to play a beneficial role in protecting the plant from potential pathogens, acquiring nutrients, and improving growth and production. Citrus is a globally important perennial fruit crop and its production faces many challenges. There has been tremendous interest in exploring the structure and function of the citrus microbiome and engineering the citrus microbiome to address various challenges. In this review, we summarized recent advances in understanding the citrus microbiome, including the composition and function of the microbiome in the rhizosphere, rhizoplane, endorhiza, and core members, and their functional traits. We conducted comparisons of the citrus root-associated microbiome with other plant root-associated microbiomes. We also present a perspective on how incoming pathogens interact with the resident microbial community and their outcomes. Despite the promising potential of the citrus microbiome to combat disease, harnessing the citrus microbiome for beneficial applications remains in its infancy. We envision that rapid development of high-throughput sequencing and multiomics technologies, artificial intelligence, consortia of microbes, genome editing technology, and high-throughput culturing present many exciting opportunities for citrus microbiome research and microbial engineering to improve citrus health and productivity.

The proposed Biology Integration Institute will bring together two major research institutions in the Upper Midwest—the University of Minnesota (UMN) and University of Wisconsin-Madison (UW)—to investigate the causes and consequences of plant biodiversity across scales in a rapidly changing world—from genes and molecules within cells and tissues to communities, ecosystems, landscapes and the biosphere. The Institute focuses on plant biodiversity, defined broadly to encompass the heterogeneity within life that occurs from the smallest to the largest biological scales. A premise of the Institute is that life is envisioned as occurring at different scales nested within several contrasting conceptions of biological hierarchies, defined by the separate but related fields of physiology, evolutionary biology and ecology. The Institute will emphasize the use of ‘spectral biology’—detection of biological properties based on the interaction of light energy with matter—and process-oriented predictive models to investigate the processes by which biological components at one scale give rise to emergent properties at higher scales. Through an iterative process that harnesses cutting edge technologies to observe a suite of carefully designed empirical systems—including the National Ecological Observatory Network (NEON) and some of the world’s longest running and state-of-the-art global change experiments—the Institute will advance biological understanding and theory of the causes and consequences of changes in biodiversity and at the interface of plant physiology, ecology and evolution.INTELLECTUAL MERITThe Institute brings together a diverse, gender-balanced and highly productive team with significant leadership experience that spans biological disciplines and career stages and is poised to integrate biology in new ways. Together, the team will harness the potential of spectral biology, experiments, observations and synthetic modeling in a manner never before possible to transform understanding of how variation within and among biological scales drives plant and ecosystem responses to global change over diurnal, seasonal and millennial time scales. In doing so, it will use and advance state-of-the-art theory. The institute team posits that the designed projects will unearth transformative understanding and biological rules at each of the various scales that will enable an unprecedented capacity to discern the linkages between physiological, ecological and evolutionary processes in relation to the multi-dimensional nature of biodiversity in this time of massive planetary change. A strength of the proposed Institute is that it leverages prior federal investments in research and formalizes partnerships with foreign institutions heavily invested in related biodiversity research. Most of the planned projects leverage existing research initiatives, infrastructure, working groups, experiments, training programs, and public outreach infrastructure, all of which are already highly synergistic and collaborative, and will bring together members of the overall research and training team.BROADER IMPACTSA central goal of the proposed Institute is to train the next generation of diverse integrative biologists. Post-doctoral, graduate student and undergraduate trainees, recruited from non-traditional and underrepresented groups, including through formal engagement with Native American communities, will receive a range of mentoring and training opportunities. Annual summer training workshops will be offered at UMN and UW as well as training experiences with the Global Change and Biodiversity Research Priority Program (URPP-GCB) at the University of Zurich (UZH) and through the Canadian Airborne Biodiversity Observatory (CABO). The Institute will engage diverse K-12 audiences, the general public and Native American communities through Market Science modules, Minute Earth videos, a museum exhibit and public engagement and educational activities through the Bell Museum of Natural History, the Cedar Creek Ecosystem Science Reserve (CCESR) and the Wisconsin Tribal Conservation Association.

ABSTRACT Soil-borne fungal phytopathogens are important threats to soil and crop health. However, their community composition and environmental determinants remain unclear. Here, we explored the effects of agricultural fertilization regime (i.e., organic material application) on soil fungal phytopathogens, using data sets from a combination of field survey and long-term experiment. We found that soil organic carbon was the key factor that affected the diversity and relative abundance of fungal phytopathogens in agricultural soils. The dominant genera of phytopathogens including Monographella was also strongly associated with soil organic carbon. In addition, the elevated soil organic carbon enhanced the node proportion of phytopathogens and the positive interactions within the fungal community in the network. Results of the long-term experiment revealed that applications of crop straw and fresh livestock manure significantly increased the proportion of phytopathogens, which were associated with the elevated soil organic carbon. This work offers new insights into the occurrence and environmental factors of fungal phytopathogens in agricultural soils, which are fundamental to control their impacts on the soil and crop systems. IMPORTANCE Fungal phytopathogens are important threats to soil and crop health, but their community composition and environmental determinants remain unclear. We found that soil organic carbon is the key factor of the prevalence of fungal phytopathogens through a field survey, which is also supported by our long-term (6-year) experiment showing the applications of crop straw and fresh livestock manure significantly increased the proportion of fungal phytopathogens. These findings advance our understanding of the occurrence and environmental drivers of soil-borne fungal phytopathogens under agricultural fertilization regime and have important implications for the control of soil-borne pathogens.

Soil age is thought to be an important driver of ecosystem development. Here, the authors perform a global survey of soil chronosequences and meta-analysis to show that, contrary to expectations, soil age is a relatively minor ecosystem driver at the biome scale once other drivers such as parent material, climate, and vegetation type are accounted for.

Aberrant regulation of developmental pathways plays a key role in tumorigenesis. Tumor cells differ from normal cells in their sustained proliferation, replicative immortality, resistance to cell death and growth inhibition, angiogenesis, and metastatic behavior. Often they acquire these features as a consequence of dysregulated Hedgehog, Notch, or WNT signaling pathways. Human tumor viruses affect the cancer cell hallmarks by encoding oncogenic proteins, and/or by modifying the microenvironment, as well as by conveying genomic instability to accelerate cancer development. In addition, viral immune evasion mechanisms may compromise developmental pathways to accelerate tumor growth. Viruses achieve this by influencing both coding and non-coding gene regulatory pathways. Elucidating how oncogenic viruses intersect with and modulate developmental pathways is crucial to understanding viral tumorigenesis. Many currently available antiviral therapies target viral lytic cycle replication but with low efficacy and severe side effects. A greater understanding of the cross-signaling between oncogenic viruses and developmental pathways will improve the efficacy of next-generation inhibitors and pave the way to more targeted antiviral therapies.

The global ecological predictors of soil priming remain unclear. Here the authors conducted a global survey of soils from 86 global locations using an isotopic approach and find that in more mesic sites with high SOC concentrations, soil priming effects are more likely to be negative.

The interdependence between thyroid hormones (THs), namely, thyroxine and triiodothyronine, and immune system is nowadays well-recognized, although not yet fully explored. Synthesis, conversion to a bioactive form, and release of THs in the circulation are events tightly supervised by the hypothalamic–pituitary–thyroid (HPT) axis. Newly synthesized THs induce leukocyte proliferation, migration, release of cytokines, and antibody production, triggering an immune response against either sterile or microbial insults. However, chronic patho-physiological alterations of the immune system, such as infection and inflammation, affect HPT axis and, as a direct consequence, THs mechanism of action. Herein, we revise the bidirectional crosstalk between THs and immune cells, required for the proper immune system feedback response among diverse circumstances. Available circulating THs do traffic in two distinct ways depending on the metabolic condition. Mechanistically, internalized THs form a stable complex with their specific receptors, which, upon direct or indirect binding to DNA, triggers a genomic response by activating transcriptional factors, such as those belonging to the Wnt/β-catenin pathway. Alternatively, THs engage integrin αvβ3 receptor on cell membrane and trigger a non-genomic response, which can also signal to the nucleus. In addition, we highlight THs-dependent inflammasome complex modulation and describe new crucial pathways involved in microRNA regulation by THs, in physiological and patho-physiological conditions, which modify the HPT axis and THs performances. Finally, we focus on the non-thyroidal illness syndrome in which the HPT axis is altered and, in turn, affects circulating levels of active THs as reported in viral infections, particularly in immunocompromised patients infected with human immunodeficiency virus.

Adipose-derived mesenchymal stem cells (ASCs) are promising therapeutic tools in regenerative medicine because they possess self-renewal, differentiation and immunomodulatory capacities. After isolation, ASCs are passaged multiple times in vitro passages to obtain a sufficient amount of cells for clinical applications. During this time-consuming procedure, ASCs become senescent and less proliferative, compromising their clinical efficacy. Here, we sought to investigate how in vitro passages impact ASC proliferation/senescence and expression of immune regulatory proteins. MicroRNAs are pivotal regulators of ASC physiology. Particularly, miR-200c is known to maintain pluripotency and targets the immune checkpoint Programmed death-ligand 1 (PD-L1). We therefore investigated its involvement in these critical characteristics of ASCs during in vitro passages. We found that when transiently expressed, miR-200c-3p promotes proliferation, maintains stemness, and contrasts senescence in late passaged ASCs. Additionally, this miRNA modulates PD-L1 and Indoleamine 2,3-Dioxygenase (IDO1) expression, thus most likely interfering with the immunoregulatory capacity of ASCs. Based on our results, we suggest that expression of miR-200c-3p may prime ASC towards a self-renewing phenotype by improving their in vitro expansion. Contrarily, its inhibition is associated with senescence, reduced proliferation and induction of immune regulators. Our data underline the potential use of miR-200c-3p as a switch for ASCs reprogramming and their clinical application.

The microbial communities associated with plants (the plant microbiome) play critical roles in regulating plant health and productivity. Because of this, in recent years, there have been significant increase in studies targeting the plant microbiome. Amplicon sequencing is widely used to investigate the plant microbiome and to develop sustainable microbial agricultural tools. However, performing large microbiome surveys at the regional and global scales pose several logistic challenges. One of these challenges is related with the preservation of plant materials for sequencing aiming to maintain the integrity of the original diversity and community composition of the plant microbiome. Another significant challenge involves the existence of multiple primer sets used in amplicon sequencing that, especially for bacterial communities, hampers the comparability of datasets across studies. Here, we aimed to examine the effect of different preservation approaches (snap freezing, fresh and kept on ice, and air drying) on the bacterial and fungal diversity and community composition on plant leaves, stems and roots from seven plant species from contrasting functional groups (e.g. C3, C4, N-Fixers, etc.). Another major challenge comes when comparing plant to soil microbiomes, as different primers sets are often used for plant vs. soil microbiomes. Thus, we also investigated if widely used 16S rRNA primer set (779F/1193R) for plant microbiome studies provides comparable data to those often used for soil microbiomes (341F/805R) using 86 soil samples. We found that the community composition and diversity of bacteria or fungi were robust to contrasting preservation methods. The primer sets often used for plants provided similar results to those often used for soil studies suggesting that simultaneous studies on plant and soil microbiomes are possible. Our findings provide novel evidence that preservation approaches do not significantly impact plant microbiome data interpretation and primer differences do not impact the treatment effect, which has significant implication for future large-scale and global surveys of plant microbiomes.

Research on plant root-associated microbial communities may help develop more efficient or sustainable crop production methods. Here the authors analyse the citrus rhizosphere microbiome, using both amplicon and deep shotgun metagenomic sequencing of samples collected across six continents.

Pathogens from the fastidious, phloem-restricted ‘Candidatus Liberibacter’ species cause the devastating Huanglongbing (HLB) disease in citrus worldwide and cause diseases on many solanaceous crops and plants in the Apiaceae family. However, little is known about the pathogenic mechanisms due to the difficulty in culturing the corresponding ‘Ca. Liberibacter’ species. Here, we report that the citrus HLB pathogen ‘Ca. L. asiaticus’ uses an active salicylate hydroxylase SahA to degrade salicylic acid (SA) and suppress plant defenses. Purified SahA protein displays strong enzymatic activity to degrade SA and its derivatives. Overexpression of SahA in transgenic tobacco plants abolishes SA accumulation and hypersensitive response (HR) induced by nonhost pathogen infection. By degrading SA, ‘Ca. L. asiaticus’ not only enhances the susceptibility of citrus plants to both nonpathogenic and pathogenic Xanthomonas citri but also attenuates the responses of citrus plants to exogenous SA. In addition, foliar spraying of 2,1,3-benzothiadiazole and 2,6-dichloroisonicotinic acid, SA functional analogs not degradable by SahA, displays comparable (and even better) effectiveness with SA in suppressing ‘Ca. L. asiaticus’ population growth and HLB disease progression in infected citrus trees under field conditions. This study demonstrates one or more pathogens suppress plant defenses by degrading SA and establish clues for developing novel SA derivatives-based management approaches to control the associated plant diseases.

Background The diet of the koala (Phascolarctos cinereus) is comprised almost exclusively of foliage from the genus Eucalyptus (family Myrtaceae). Eucalyptus produces a wide variety of potentially toxic plant secondary metabolites which have evolved as chemical defences against herbivory. The koala is classified as an obligate dietary specialist, and although dietary specialisation is rare in mammalian herbivores, it has been found elsewhere to promote a highly-conserved but low-diversity gut microbiome. The gut microbes of dietary specialists have been found sometimes to enhance tolerance of dietary PSMs, facilitating competition-free access to food. Although the koala and its gut microbes have evolved together to utilise a low nutrient, potentially toxic diet, their gut microbiome has not previously been assessed in conjunction with diet quality. Thus, linking the two may provide new insights in to the ability of the koala to extract nutrients and detoxify their potentially toxic diet. Method The 16S rRNA gene was used to characterise the composition and diversity of faecal bacterial communities from a wild koala population (n = 32) comprising individuals that predominately eat either one of two different food species, one the strongly preferred and relatively nutritious species Eucalyptus viminalis, the other comprising the less preferred and less digestible species Eucalyptus obliqua. Results Alpha diversity indices indicated consistently and significantly lower diversity and richness in koalas eating E. viminalis. Assessment of beta diversity using both weighted and unweighted UniFrac matrices indicated that diet was a strong driver of both microbial community structure, and of microbial presence/absence across the combined koala population and when assessed independently. Further, principal coordinates analysis based on both the weighted and unweighted UniFrac matrices for the combined and separated populations, also revealed a separation linked to diet. During our analysis of the OTU tables we also detected a strong association between microbial community composition and host diet. We found that the phyla Bacteroidetes and Firmicutes were co-dominant in all faecal microbiomes, with Cyanobacteria also co-dominant in some individuals; however, the E. viminalis diet produced communities dominated by the genera Parabacteroides and/or Bacteroides, whereas the E. obliqua-associated diets were dominated by unidentified genera from the family Ruminococcaceae. Discussion We show that diet differences, even those caused by differential consumption of the foliage of two species from the same plant genus, can profoundly affect the gut microbiome of a specialist folivorous mammal, even amongst individuals in the same population. We identify key microbiota associated with each diet type and predict functions within the microbial community based on 80 previously identified Parabacteroides and Ruminococcaceae genomes.

Conventional/targeted chemotherapies and ionizing radiation (IR) are being used both as monotherapies and in combination for the treatment of epithelial ovarian cancer (EOC). Several studies show that these therapies might favor oncogenic signaling and impede anti-tumor responses. MiR-200c is considered a master regulator of EOC-related oncogenes. In this study, we sought to investigate if chemotherapy and IR could influence the expression of miR-200c-3p and its target genes, like the immune checkpoint PD-L1 and other oncogenes in a cohort of EOC patients’ biopsies. Indeed, PD-L1 expression was induced, while miR-200c-3p was significantly reduced in these biopsies post-therapy. The effect of miR-200c-3p target genes was assessed in miR-200c transfected SKOV3 cells untreated and treated with olaparib and IR alone. Under all experimental conditions, miR-200c-3p concomitantly reduced PD-L1, c-Myc and β-catenin expression and sensitized ovarian cancer cells to olaparib and irradiation. In silico analyses further confirmed the anti-correlation between miR-200c-3p with c-Myc and β-catenin in 46 OC cell lines and showed that a higher miR-200c-3p expression associates with a less tumorigenic microenvironment. These findings provide new insights into how miR-200c-3p could be used to hold in check the adverse effects of conventional chemotherapy, targeted therapy and radiation therapy, and offer a novel therapeutic strategy for EOC.

Plant health and productivity is strongly influenced by their intimate interaction with deleterious and beneficial organisms, including microbes and insects. Of the various plant diseases, insect-vectored diseases are of particular interest, including those caused by obligate parasites affecting plant phloem such as Candidatus (Ca.) Phytoplasma species and several species of Ca. Liberibacter. Recent studies on plant-microbe and plant-insect interactions of these pathogens have demonstrated that plant-microbe-insect interactions have far reaching consequences for the functioning and evolution of the organisms involved. These interactions take place within complex pathosystems and are shaped by a myriad of biotic and abiotic factors. However our current understanding of these processes and their implications for the establishment and spread of insect-borne diseases remains limited. This article highlights the molecular, ecological, and evolutionary aspects of interactions among insects, plants, and their associated microbial communities with a focus on insect vectored and phloem-limited pathogens belonging to Ca. Phytoplasma and Ca. Liberibacter species. We propose that innovative and interdisciplinary research aimed at linking scales from the cellular to the community level will be vital for increasing our understanding of the mechanisms underpinning plant-insect-microbe interactions. Examination of such interactions could lead us to applied solutions for sustainable disease and pest management.

Agricultural intensification is placing tremendous pressure on the soil’s capacity to maintain its functions leading to large-scale ecosystem degradation and loss of productivity in the long term. Therefore, there is an urgent need to find early-indicators of soil health degradation in response to agricultural management. In recent years, major advances in soil meta-genomic and spatial studies on microbial communities and community-level molecular characteristics can now be exploited as ‘biomarker’ indicators of ecosystem processes for monitoring and managing sustainable soil health under global change. However, a continental scale, cross biome approach assessing soil microbial communities and their functional potential is essential to identify the unifying principles governing the susceptibility of soil biodiversity to land conversion is lacking. Herein we conducted a meta-analysis from a dataset generated from 102 peer-reviewed publications as well as unpublished data to explore how properties directly linked to soil nutritional health ( total C and N; C:N ratio), primary productivity (NPP) and microbial diversity and composition (relative abundance of major bacterial phyla determined by next generation sequencing techniques) are affected in response to agricultural management across the main biomes of Earth (arid, continental, temperate and tropical). In our analysis, we found strong statistical trends in the relative abundance of several bacterial phyla in agricultural (e.g. Actinobacteria and Chloroflexi) and natural (Acidobacteria, Proteobacteria, and Cyanobacteria) systems across all regions and these trends correlated well with many soil properties. However, main effects of agriculture on soil properties and productivity were biome-dependent. Our meta-analysis provides evidence on the predictable nature of the microbial community responses to vegetation type. This knowledge can be exploited in future for developing a new set of indicators for primary productivity and soil health.

Understanding the mechanisms of autophagy induction and its role during chemotherapeutic treatments is of fundamental importance in order to manipulate it to improve the outcome of chemotherapy. In particular whether the bortezomib-induced autophagy plays a pro-survival or pro-death role is still controversial. In this study we investigated if bortezomib induced endoplasmic reticulum (ER) stress and activated autophagy in Primary Effusion Lymphoma (PEL) cells and how they influenced cell survival. We found that bortezomib induced up-regulation of the pro-survival and pro-death ER stress molecules BIP and CHOP and activated c-Jun NH2-terminal kinase (JNK), resulting in Bcl-2 phosphorylation and induction of autophagy. JNK and autophagy activation played a pro-survival role in this setting, thus their inhibition increased the bortezomib cytotoxic effect and PARP cleavage in PEL cells. Based on our results we suggest that the combination of bortezomib with JNK or autophagy inhibitors could be exploited to improve the outcome of therapy of this aggressive B cell lymphoma.

To understand how cytotoxic agent-induced cancer cell death affects the immune system is of fundamental importance to stimulate immune response to counteract the high mortality due to cancer. Here we compared the immunogenicity of Primary Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments were able to induce PEL apoptosis with similar kinetics and promote dendritic cells (DC) maturation. The surface expression of molecules involved in immune activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70 increased in dying cells. This was correlated with DC activation. We found that PEL cell death induced by Bortezomib was more effective in inducing uptake by DC compared to AG 490 or combination of both drugs. However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL cells, as seen in the present study, might have important implications for a combined chemo and immunotherapy in such patients.