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mhryu@live.com
Today, 12:50 AM
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Biological discoveries in plant and human systems have long advanced our understanding of how signaling, metabolism, and immunity shape cross-kingdom interactions. Building on this rich history of interdisciplinary insight, there is now a tremendous opportunity to strengthen connections between human and agricultural microbiome research. This perspective highlights key biological synergies across these systems that are essential for advancing human, agricultural, and ecosystem health. Focus is given to colonization, immune, and biosafety engineering strategies developed for microbiome therapeutics that can guide the design and development of next-generation agricultural bioproducts. Ultimately, greater knowledge exchange and collaboration across disciplines will be critical to translate microbiome discoveries into bioproducts with positive societal impact.
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Scooped by
mhryu@live.com
Today, 12:38 AM
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Microbially mediated hydrocarbon biodegradation is a cornerstone of natural attenuation and engineered bioremediation, yet the in situ mechanisms and key microbial players remain incompletely resolved due to the historical reliance on cultivation-based approaches. Recent advances in cultivation-independent tools, particularly metagenomics, stable isotope probing (SIP), and single-cell techniques, now enable more effective identification of active microbial populations, their functional genes, and metabolic networks directly mediating hydrocarbon degradation in situ. These studies have unveiled a far greater phylogenetic and functional diversity than previously recognized, including the unexpected co-existence of alkane-oxidizing archaea and bacteria in similar environments. The underlying microbial actors exploit distinctive enzymes to initialize hydrocarbon oxidation under oxic and anoxic conditions and achieve complete degradation through complex ecological networks that involve cooperative and/or competitive interactions with other community members such as viruses. These findings offer better insights into the functioning of the microorganisms that control the fate of hydrocarbons in situ and, as a final outcome, help tailor bioremediation strategies for better performance.
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mhryu@live.com
Today, 12:14 AM
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Organic contaminants from natural and anthropogenic sources threaten global water and food security. While bioremediation offers significant mitigation potential, tracking compound degradation in complex ecosystems remains challenging. Detection technologies span from microscale methods — biosensors, imaging, and volatile organic analysis — to landscape-scale remote sensing. Each technique provides unique information, but integrating these disparate data streams is a major bottleneck hindering ecological-scale tracking and assessment. In this review, we propose a holistic monitoring framework for detecting contaminants and tracking the progress of bioremediation, highlighting minimally invasive detection techniques and cross-scale sensor integration. We discuss emerging technologies and the generation of standardized datasets essential for machine-learning applications in predicting degradation trajectories using fabricated ecosystems. Integrating environmental sensing, microbiome science, and advanced analytics provides a new chassis for interrogating remediation efforts.
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mhryu@live.com
February 25, 11:42 PM
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Liquid-liquid phase-separation (LLPS) controls protein activity and dynamically organizes (macro)molecules in living systems without the need for membrane-bound compartments. Biomolecular condensates of water-soluble proteins have extensively been studied, but little is known about LLPS of membrane proteins. In this work we induce in vivo condensation of lactose permease (LacY), a widely-studied model monomeric inner membrane protein in E. coli, and evaluate how it affects LacY function. We fused LacY with engineered, condensate-forming protein PopTag. We observe major changes in the localization and mobility of LacYPop. Molecular dynamics simulations show how the PopTag domain drives the condensate-like association dynamics of LacYPop through hydrophobic sticker interactions. LacYPop preserves native-level transport activity and outperforms the non-condensed LacY under mild hyperosmotic stress (osmotic upshift). In osmotically stressed cells, membrane-bound biomolecular condensates also reduce deformation of the cytoplasmic membrane. Perturbation experiments suggest that membrane curvature drives the accumulation of LacYPop at the poles of E. coli. Co-condensation of LacY and β-galactosidase LacZ slightly reduces their activity and results in remarkable cellular reorganization of the proteins. Our research shows the localization, dynamics, and function of phase-separated membrane proteins in bacteria and highlights the potential of LLPS for engineering complex metabolic networks in vivo. Phase-separation of the transport protein LacY alters its membrane localization and mobility, preserves its transport activity, reduces cell membrane stress under osmotic upshift, and LacY forms mixed condensates with the enzyme β-galactosidase LacZ.
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mhryu@live.com
February 25, 11:31 PM
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RNA base editing using engineered deaminases represents a powerful tool to correct mutations at the RNA level. However, widespread off-target effects, primarily arising from dissociated free deaminases, remain a significant challenge. Here, we devise the RECODE (RNA editing with conditionally stable and enhanced ADAR1 deaminase variants) system, which employs designer degron-tagged ADAR1 deaminase (ADAR1d) with guide RNA (gRNA)-regulated stability. By promoting degradation of gRNA-unbound ADAR1d, RECODE markedly reduces transcriptome-wide edits while maintaining high on-target efficacy. Engineering gRNA for target RNA-induced conformational switching confines ADAR1d stabilization to intended editing sites, further enhancing editing precision. With structure-guided rational engineering of ADAR1d, RECODE efficiently corrects an Amyotrophic Lateral Sclerosis-relevant FUS mutation and installs a therapeutic mutation to Angptl3 in vivo, which mitigate FUS mislocalization to neuronal axons and lower plasma lipids, respectively. These findings establish RECODE as a highly stringent and efficient RNA editing technology and underscore a general principle for enhancing the specificity of RNA-guided protein effectors. Engineered RNA base editors are powerful yet limited by promiscuous deaminase activity. Here, the authors devise RECODE that enforces target-dependent deaminase stabilization, thereby reducing off-target edits, and achieving effective in vivo editing of FUS and Angptl3.
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Scooped by
mhryu@live.com
February 25, 11:12 PM
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a, Animals and close relatives of animals (such as Salpingoeca rosetta) become multicellular through a clonal process in which genetically identical cells divide and remain attached to each other. b, In lineages that are more-distant relatives of animals (such as Capsaspora owczarzaki), genetically distinct cells (genetic lineages are shown in different colors) assemble together to become multicellular in what’s known as an aggregative process. c, Ros-Rocher et al.1 reveal that Choanoeca flexa can become multicellular through both clonal and aggregative processes, as well as by a mixture of both. Cues from the natural environment, such as the level of salinity and density of cells in the splash pools where it grows, regulate the transition of C. flexa to multicellularity from a unicellular form called a cyst, which can become free-swimming when water is present.
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mhryu@live.com
February 25, 10:54 PM
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Antibiotic resistance is a growing health issue, and novel peptide antibiotics like non-ribosomal peptides (NRPs) potentially play a key role in countering bacteria that are resistant to existing antibiotics. However, NRPs are not gene-encoded, making it difficult to generate and screen mutant libraries. In contrast, biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs) offers a gene-encoded platform enabling diverse modifications that can mimic NRP structures. By engineering peptide sequences and utilizing RiPP-modifying enzymes, it is possible to create tailor-made antimicrobial peptides. This highlights the potential of RiPP-based systems for activity-based screening and the discovery of novel antibiotics. In this study, E. coli surface display and co-culture techniques were employed to extracellularly produce intracellularly modified RiPPs. After intracellular modification by OspR to introduce ornithine at selected positions and SyncM to introduce a methyllanthionine ring (MeLan), a modified precursor Brevicidine-mimicking mutant peptide (Bre-re-mutant) was displayed by the surface display proteins of Lpp-OmpA and Omp1. In separate cells leader peptidase LahT150 was displayed with InaK. InaK is a type of ice nucleating protein, which enables to display relatively large proteins. Following co-culture of E. coli expressing and displaying the Bre-re-mutant with E. coli expressing the displayed leader peptidase LahT150, the aimed for modified peptide was successfully detected in the supernatant and its antimicrobial activity was assessed. Additionally, the display efficiency of Lpp-OmpA and Omp1 was evaluated, showing a maximum display efficiency of over 90%. This method shows potential for the quick and accurate assessment of in E. coli modified peptides and their antimicrobial activity, facilitating advancements in research and eventual industrial applications.
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mhryu@live.com
February 25, 10:28 PM
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Plants produce antibiotic substances and bacteria need to cope with those substances to colonize plants. We analyzed the inventory of genes encoding resistance-nodulation-cell division (RND) efflux pumps originating from 282 bacterial isolates from leaves or roots of the model plant Arabidopsis thaliana. We confirmed that, on average, plant associated bacteria hold a significantly increased repertoire of genes encoding RND antiporters homologs compared to strains isolated from other ecological niches, as reported in a previous study. While some RND antiporter clades were enriched in plant colonizers, other clades found in the genomes of isolates from other environments were underrepresented. An in-depth analysis of RND antiporters from plant colonizing bacteria revealed that conserved motifs can be found in each clade, possibly contributing to substrate specificity. Interestingly, we found horizontal gene transfer markers in 10% of the antiporter homologs, suggesting that horizontal gene transfer may significantly contribute to the adaptation of bacteria to the specific chemical environment created by different organs of plant hosts. In addition, homologs from leaf-isolated bacteria showed a lower diversification, and harbored markers of horizontal gene transfer in the heavy metal exporting clade. Sequence and structural analysis revealed a high diversity in RND-antiporters, with few residues under purifying selection, indicating that RND diversity is driven by random mutations. Our findings have major implications for the origin of multidrug resistances and for our understanding of the forces shaping the outcome of plant-microbe ecology in general.
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mhryu@live.com
February 25, 10:03 PM
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Understanding and predicting bacterial substrate preferences has broad utility from microbial interactions to selecting prebiotics. Isolate exometabolite profiling directly measures which compounds a given microbe utilizes from an array of metabolites in the environment. However, modeling, mining, and integrating these data are challenging. Here, we introduce a Bayesian Personalized Ranking (BPR) model applied to substrate preferences which we find learns to rank compounds by a given microbial preference. It was found to outperform the other ranking models (AUC = 0.93), proved robust to ablation, showed strong within-genus isolate pairs correlation (Spearman rank = 0.78) and predictive ability for new data. BPR was then used to create the Web of Microbes (WoM) Agent by integrating it with the Phydon growth model and Large Language Model (LLM) for autonomous orchestration tool calling and analysis. The WoM Agent accurately predicted substrate consumption by existing strain grown on a novel medium and correctly identified bacteria enriched in soil metabolite spike-in experiments. Additionally, the WoM Agent can use autonomous reasoning including to predict substrates that will selectively promote the growth of one clade of bacteria over another including helping interpret results and suggest new hypotheses and experiments. We anticipate broad applications in microbial cultivation, microbiome engineering, and environmental microbiology and that these capabilities will be extensible through the integration of additional tools and use of rapidly improving LLMs.
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mhryu@live.com
February 25, 7:50 PM
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Fecal microbiota transplantation (FMT) has shown immunotherapeutic promise, yet its efficacy in non-small-cell lung cancer (NSCLC) remains unclear. We demonstrate that FMT improves anti-PD-1 efficacy and progression-free survival in a single-arm trial of advanced PD-L1-negative NSCLC. Analyzing over 2,000 metagenomes from diverse disease cohorts and healthy controls via a high-resolution strain-tracking framework, we reveal that phylogenetically distinct strains within identical species exert opposing therapeutic effects, resolving prior inconsistencies. We identify conserved ecological principles where engraftment relies on species-intrinsic metabolic and immune evasion traits. Crucially, successful colonization by specific beneficial strain variants correlates with positive clinical outcomes. Finally, we identify 38 priority species with robust engraftment potential and significant heterogeneity as candidates for precision therapeutics. These findings establish a strain-function-efficacy paradigm, elucidating the mechanistic basis of variable outcomes and guiding next-generation microbiome drug development.
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Scooped by
mhryu@live.com
February 25, 6:35 PM
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Rhizosphere microbiota mediate plant defense against soil-borne diseases, yet the mechanisms by which resistant soybean cultivars assemble protective microbiomes remain poorly understood. Using metagenomics, metabolomics, in vitro assays, and genetic approaches, we compared near-isogenic lines (Williams82, resistant; Williams, susceptible) to dissect plant–metabolite–microbe interactions mediating Phytophthora root rot (PRR) resistance. Transplanting rhizosphere soil from the resistant cultivar to susceptible plants significantly reduced PRR severity, correlating with Pseudomonas enrichment and accumulation of the key rhizosphere metabolite 3,4-dihydroxybenzaldehyde. We isolated a core beneficial strain, Pseudomonas parafulva ZY6, from the resistant rhizosphere. In vitro, 3,4-dihydroxybenzaldehyde treatment promoted ZY6’s biofilm formation, motility, and growth, while inhibiting Phytophthora sojae at higher concentrations. Knockout and overexpression of GmTL29 via hairy root transformation altered rhizosphere levels of 3,4-dihydroxybenzaldehyde, which in turn modulated the colonization of ZY6, the abundance of P. sojae, and the relative abundance of beneficial taxa such as Pseudomonas. Exogenous 3,4-dihydroxybenzaldehyde (0.1 μmol·g-1 soil) significantly reduced PRR disease index, increased rhizosphere bacterial diversity, and enriched Bacillus and Pseudomonas. Our study demonstrates that resistant soybeans shape a disease-suppressive rhizosphere, in which 3,4-dihydroxybenzaldehyde contributes as a prebiotic by selectively enriching beneficial microbes. These findings offer a metabolite-based strategy to engineer rhizosphere communities for sustainable soil-borne disease management.
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mhryu@live.com
February 25, 6:21 PM
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GenomeDepot is an open-source web-based platform for annotation, management, and comparative analysis of microbial genomic sequences and associated data including ortholog families, protein domains, operons, regulatory interactions, strain taxonomy, and sample metadata. GenomeDepot supports rapid creation of websites for user-defined genome collections that include bioinformatic tools for interactive genome browsing, Basic Local Alignment Search Tool (BLAST) search, annotation search, comparative genomic neighborhood visualization, and sequence download. Gene function annotations are generated by a customizable annotation pipeline. The pipeline runs annotation tools in Conda environments and can be easily extended with additional user-specified tools.
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Scooped by
mhryu@live.com
February 25, 6:10 PM
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T7 RNA polymerase (T7 RNAP) is the most widely used enzyme for synthesizing therapeutic mRNA. However, RNA transcribed by T7 RNAP often contains double-stranded RNA (dsRNA) by-products that trigger innate immune responses and complicate purification. Here, we report an engineered T7 RNAP variant, M30, which exhibits higher catalytic efficiency and reduced dsRNA by-product formation. M30 was developed through 4 rounds of directed evolution using an ultrahigh-throughput aptamer-based fluorescence-activated droplet sorting system. M30 displays a 10-fold increase in catalytic efficiency over wild-type T7 RNAP at 37 °C, along with markedly enhanced thermostability and approximately 10-fold lower production of dsRNA by-products. mRNAs synthesized with M30 achieve efficient protein expression in human cells and in mice, while eliciting reduced immunogenicity compared with mRNAs produced by wild-type T7 RNAP. Biophysical assays and structural analyses suggest that these improvements result from increased DNA template binding affinity and decreased RNA binding affinity. Together, these features make M30 a promising catalyst for high-quality therapeutic mRNA production.
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Scooped by
mhryu@live.com
Today, 12:48 AM
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Asexual reproduction in filamentous fungi is a common, efficient, and fast differentiation process for producing large numbers of asexual spores (conidia), which can be distributed through the air to colonize new environments. The whole process is tightly controlled by specific regulatory proteins. Among the major regulators is the zinc cluster protein of SclB (sclerotia-like B), known to influence various aspects of asexual growth and secondary metabolism in Aspergillus nidulans as well as other filamentous fungi. Two different growth conditions of A. nidulans were compared to obtain a mechanistic overview of the role of SclB, mainly during the transition of the fungus from vegetative to asexual growth. Chromatin immunoprecipitation (IP) was coupled with next-generation sequencing (ChIP-seq) and combined with transcriptomic analyses (RNA-seq). SclB coordinates this developmental shift mainly by controlling the expression of genes encoding a few, however, prominent regulators of conidiation. These include the transcription factors BrlA, VelB, and SclB and the pheromone oxygenase PpoC. Association of SclB to promoter regions requires the newly identified putative SclB response element with a nine-base-pair DNA motif. Scl2 is the corresponding protein in the fungal plant pathogen Verticillium dahliae and partially complements the A. nidulans ΔsclB asexual deficiency. This supports a partial functional complementation of this regulator among different fungal species. In summary, SclB coordinates the transition from vegetative growth to asexual reproduction in A. nidulans through in vivo transcriptional control over genes coding for established players of conidia formation.
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Scooped by
mhryu@live.com
Today, 12:29 AM
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CBASS is an immune pathway that recognizes phage infection and generates cyclic nucleotide signals, which directly activate effectors that stop phage replication. Membrane-acting effectors are proposed to induce cell death to prevent phage replication; however, this mechanism has not been assessed with endogenous expression levels of the effector. We therefore sought to determine the cell viability outcomes of the CBASS phospholipase effector (CapV) upon activation with 3',3'-cGAMP signals in Pseudomonas aeruginosa. Here, we surprisingly observe that constitutive 3',3'-cGAMP signaling from the synthase (CdnA) enables robust cell growth and viability while effectively abolishing phage production in a CapV-dependent manner. Exogenous 3',3'-cGAMP also enhances CBASS antiphage activity and cell growth. Moreover, constitutive activation of the CapV effector induces no cell fitness cost, and blocks replication of many, but not all, phages. This demonstrates that a cyclic nucleotide-activated CBASS effector possess a degree of phage specificity that has been previously overlooked. When CBASS is active, phage transcription and initiation of DNA replication proceed normally, but phages do not reach maximum DNA levels and fewer mature virions are produced. Based on these findings, we propose that CapV interferes with the early stages of phage capsid assembly at the cell membrane and resultantly disrupts DNA packaging. Collectively, we demonstrate that a successful CBASS response antagonizes a late-stage of the phage replication cycle while maintaining cell viability.
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Scooped by
mhryu@live.com
February 25, 11:53 PM
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This review summarizes recent advances in the metabolic engineering of microorganisms for the valorization of C2 feedstocks into high-value chemicals and materials. We first discuss native and engineered C2 assimilation pathways, including reverse β-oxidation, aldol-condensation-based carbon extension, and thiamine pyrophosphate-dependent modules, highlighting representative strain designs in E. coli, Pseudomonas spp., and photosynthetic hosts. We then examine C1-to-C2 platform strategies that couple acetogens or gas-fermenting microbes with C2-assimilating production strains. Finally, we outline the rapidly growing toolbox of non-natural and computationally designed pathways that rewire carbon flux with minimal loss. Particular emphasis is placed on the integration of synthetic biology, enzyme engineering, genome-scale metabolic models, and artificial intelligence-driven design for building next-generation, electrified, and digitally guided C2 biorefineries. These advances are positioning C2-based biomanufacturing as a key pillar of low-carbon chemical production.
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mhryu@live.com
February 25, 11:32 PM
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Nano-zymes have progressed from simple enzyme mimics to a versatile class of artificial catalysts that expand functionality beyond the reach of natural enzymes. In this Perspective, we examine how the materials design of nanozymes enables catalytic behaviors that are inaccessible to biological systems, including activity in non-biological environments, promotion of non-natural reactions and the integration of multiple catalytic functions within a single nanostructure. Through nanoscale control over physicochemical parameters and emulation of key enzyme architectures, nanozymes can achieve finely tunable activity and selectivity. Facile surface functionalization and inherent electrical connectivity further enhance their performance in complex systems. Collectively, these attributes extend catalysis beyond the constraints of natural enzymes, driving innovations in an array of different fields, including biomedicine, agriculture, environmental remediation and energy conversion. Nanocatalyst ‘nanozymes’ provide a versatile alternative to natural enzymes. Nanozymes can operate in conditions inimical to enzymes and can catalyse reactions that their natural analogues cannot. This Perspective discusses design principles, strengths, challenges and applications of nanozymes.
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Scooped by
mhryu@live.com
February 25, 11:14 PM
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Polyethylene terephthalate (PET) is one of the most widely used plastics, yet recycling relies on energy-intensive chemical processes with environmental burdens. As an alternative, PET hydrolytic enzymes such as PET hydrolase (PETase) from Piscinibacter sakaiensis have been proposed for biological PET recycling under mild conditions. Inspired by recent studies on plastic degradation by insects, here we explored genetically engineered insects as a platform for PET biodegradation. We heterologously expressed PETase in the fruit fly Drosophila melanogaster, targeting a subset of the intestinal tract and the salivary glands. PETase-expressing flies degraded both a water-soluble PET copolymer in vivo and solid PET in the surrounding environment under alkaline conditions. Notably, the secreted PETase was glycosylated, reducing catalytic activity but enhancing stability and enabling prolonged PET degradation. These findings demonstrate a proof of concept for the application of engineered insects in plastic biodegradation and suggest new directions for sustainable, biology-based recycling technologies. Polyethylene terephthalate (PET) hydrolase from Piscinibacter sakaiensis was expressed in Drosophila melanogaster, generating an insect model that enables PET degradation in vivo and in the surrounding environment.
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mhryu@live.com
February 25, 10:58 PM
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Coral reefs are marine biodiversity hotspots that provide a wide range of ecosystem services. They are reservoirs of bioactive metabolites, many produced by microorganisms associated with reef invertebrate hosts. However, for the keystone species of coral reefs—the reef-building corals—we still lack a systematic assessment of their microbially encoded biosynthetic potential and the molecular resources at stake due to the alarming decline in reef biodiversity. Here we analysed microbial genomes reconstructed from 820 reef-building coral samples of three representative coral genera collected at 99 reefs across 32 islands throughout the Pacific Ocean (Tara Pacific expedition). By contextualizing our analyses with the microbiomes of other reef species, we found that only 10% of the 4,224 microbial species and less than 1% of the 645 species exclusively identified in Tara Pacific samples had genomic information available. Furthermore, the biosynthetic potential of reef-building coral microbiomes rivalled or surpassed that of traditional natural product sources such as sponges. Among the biosynthetically rich bacteria in the reef microbiome, we identified new groups of Acidobacteriota that encode previously unknown enzymology, in turn opening promising avenues for functional protein engineering. Together, this study underscores the importance of conserving coral reefs as vital reservoirs of molecular diversity. Reconstructing microbial genomes from 820 reef-building corals collected at 99 reefs across 32 islands throughout the Pacific Ocean highlights the importance of conserving coral reefs as vital reservoirs of molecular diversity.
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mhryu@live.com
February 25, 10:32 PM
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Enabling heterotrophic E. coli to use CO2 as its only carbon source remains a great challenge, and previous studies approached autotrophy conversion by metabolic engineering. Although its native carbon fixation routes were identified, the potential to reach autotrophy by itself has long been overlooked. In this study, autotrophy in E. coli was developed through adaptive laboratory evolution. After 1,000 days of consecutive inorganic subculturing, missense mutations were found in isocitrate dehydrogenase icd and isocitrate dehydrogenase kinase/phosphatase aceK, determining the metabolic switch between the citrate cycle and the glyoxylate shunt. By transcriptomic comparison of the adapted E. coli between inorganic and organic cultivations, two CO2 fixing enzymes activated in autotrophic mode were found, including the upregulated pyruvate:ferredoxin oxidoreductase YdbK and phosphoenolpyruvate carboxykinase Pck. Connected by the upregulated phosphoenolpyruvate synthase PpsA, a carbon fixation module was constituted, which was the shared foundation of the aspartate-threonine cycle and the citrate-glyoxylate-methylcitrate cycle, and thus integrating into an autotrophic network. By comparing the 13C enrichment patterns in inorganic cultivations between the adapted and initial E. coli, the favorable direction of the autotrophic network was confirmed.
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mhryu@live.com
February 25, 10:23 PM
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Antimicrobial resistance (AMR) is accelerating worldwide, undermining frontline antibiotics and making the need for novel agents more urgent than ever. Antimicrobial peptides (AMP) are promising therapeutics against multidrug-resistant pathogens, as they are less prone to inducing resistance. However, current AMP prediction approaches often treat sequence and structure in isolation and at a single scale, leading to mediocre performance. Here, we propose MultiAMP, a framework that integrates multi-level information for predicting AMPs. The model captures evolutionary and contextual information from sequences alongside global and fine-grained information from structures, synergistically combining these features to enhance predictive power. MultiAMP achieves state-of-the-art performance, outperforming existing methods by over 10\% in MCC when identifying distant AMPs sharing less than 40\% sequence identity with known AMPs. To discover novel AMPs, we applied MultiAMP to marine organism data, discovering 484 high-confidence peptides with sequences that are highly divergent from known AMPs. Notably, MultiAMP accurately recognizes various structural types of peptides. In addition, our approach reveals functional patterns of AMPs, providing interpretable insights into their mechanisms. Building on these findings, we employed a gradient-based strategy and achieved the design of AMPs with specific motifs. We believe MultiAMP empowers both the rational discovery and mechanistic understanding of AMPs, facilitating future experimental validation and therapeutic design. The codebase is available at \url{https://github.com/jiayili11/multi-amp}.
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mhryu@live.com
February 25, 7:56 PM
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Prokaryotic Argonaute proteins (pAgos) are emerging as versatile tools in nucleic acid processing; however, their roles in bacterial physiology remain poorly defined. Here, we demonstrate that overexpression of Thermus thermophilus Argonaute (TtAgo) promotes transient bacterial filamentation in both T. thermophilus and E. coli through disruption of cell division checkpoints. Scanning electron microscopy and nucleoid DNA staining revealed defective septum formation and aberrant nucleoid segregation in filamentous cells. By observing the effect of truncated TtAgo variants on septum formation and nucleoid segregation in E. coli, we found that impairment of septum formation in the filamentous cells was independent of the DNA cleavage activity of the TtAgo protein. Further, we demonstrate that TtSSB interacts with TtAgo and recruits it to the replication fork, where it facilitates the DNA-binding activity of TtAgo. TtAgo acquires short DNA guides from broken double-stranded DNA and cleaves complementary chromosomal sequences, leading to DNA damage and filamentation. This filamentation triggers homologous recombination-mediated repair in T. thermophilus, allowing cells to return to a rod-shaped state. These findings reveal a mechanism by which the SSB-TtAgo interaction can modulate the bacterial cell cycle and DNA repair pathways, highlighting its potential for synthetic biology and biotechnology applications.
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mhryu@live.com
February 25, 6:41 PM
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Carbon catabolite repression (CCR) acts as a switch, reprogramming nutrient utilization in fungal pathogens during the growth-to-colonization transition. However, whether this regulatory system can be exploited by other microbes remains unknown. Here, we demonstrate that Pseudomonas CXZ-8 attenuates the virulence of Fusarium graminearum by hijacking fungal CCR. CXZ-8 disrupts the infection-induced nuclear-to-cytoplasmic relocalization of the CCR master regulator FgCreA, thereby suppressing FCO1 expression, which is crucial for both host cell wall degradation and nutrient acquisition. This interference also benefits the bacterium by preventing the accumulation of host-derived indole derivatives and fungal mycotoxins that threaten its survival. Notably, approximately 20% of field-isolated bacteria exhibit similar FgCreA-stabilizing activity. Furthermore, we assembled a microbial consortium enriched for CCR-targeting bacteria, which conferred broad-spectrum disease resistance in field trials. These findings reveal a novel mode of interkingdom interference and establish CCR as a conserved microbial vulnerability, with implications for sustainable, microbiome-based crop protection.
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mhryu@live.com
February 25, 6:24 PM
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The advent of ribosome profiling (an adaptation of RNA sequencing) to determine the translatome, has led to a huge improvement in our understanding of what parts of the transcriptome are translated. Many alternative open reading frames (ORFs) are now regularly being detected such as out-of-frame, overlapping, upstream or downstream reading frames, and alternative reading frames using non-canonical start codons. Various tools have been developed for the detection of such novel ORFs, but they lack the capacity to visually inspect reads—an important aspect of validation and prediction of translation. The integrated and visualization of ribosome profiling and RNA sequencing reads enables discrimination between transcriptional and translational signals, facilitating validation of predicted novel open reading frames. Furthermore, the inclusion of complementary evidence such as proteomic and long-read sequencing enables further validation of predicted novel open reading frames. Here, we present, InspectorORF (https://www.github.com/aylz83/inspectorORF), an R package that readily plots ribosome profiling reads, alongside RNA sequencing reads across transcripts and/or ORFs. Additionally, custom information can be plotted including data from additional conditions and samples, proteomic analyses and reads from long-read sequencing.
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Scooped by
mhryu@live.com
February 25, 6:16 PM
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Understanding macromolecular structures of proteins and nucleic acids is critical for discerning their functions and biological roles. Advanced techniques—crystallography, nuclear magnetic resonance, and cryo–electron microscopy—have facilitated the determination of more than 180,000 protein structures, all cataloged in the Protein Data Bank. This comprehensive repository has been pivotal in developing deep learning algorithms for predicting protein structures directly from sequences. In contrast, RNA structure prediction has lagged and suffers from a scarcity of structural data. Here, we present the secondary structure models of 1098 primary microRNAs and 1456 human messenger RNA regions determined through chemical probing. We develop a deep learning architecture inspired from the Evoformer model of Alphafold and traditional architectures for secondary structure prediction. This model, eFold, was trained on our newly generated database and more than 300,000 secondary structures across multiple sources. We benchmark eFold on two challenging test sets of long and diverse RNA structures and show that our dataset and architecture contribute to increasing the prediction performance, compared to similar state-of-the-art methods. Together, our results reveal that merely expanding the database size is insufficient for generalization across families, whereas incorporating a greater diversity and complexity of RNA structures allows for enhanced model performance.
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2st, Here, we describe the Web of Microbes Agent (WoM Agent), currently available at http://webofmicrobes.org/, which combines an LLM with a Bayesian Personalized Ranking (BPR) model of substrate preferences and a growth model.