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mhryu@live.com
February 1, 1:35 PM
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MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression. Their dysregulation is closely associated with various diseases, positioning them as biomarkers of cellular state. Synthetic biology has leveraged these properties to engineer miR-based genetic circuits capable of sensing and interpreting endogenous miR levels. Early miR-OFF systems relied on reporter gene repression but were limited by ambiguous signal interpretation. Subsequent advances introduced miR-ON architectures, logic-based classifiers integrating multiple miRs, and layered regulatory strategies combining transcriptional, translational, and cleavage-based modules to enhance sensitivity and specificity. Recent innovations include CRISPR-associated miR-responsive systems and incoherent feed-forward loop (iFFL) architectures that stabilize gene expression amid cellular variability, shifting applications from passive sensing to therapeutic intervention. Despite challenges such as leakage, cellular resource resources, and delivery, progress in orthogonal miR toolkits, computational modeling, and RNA-based delivery platforms is rapidly driving miR-based circuits toward diagnostic and therapeutic applications.
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mhryu@live.com
February 1, 1:24 PM
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Invasive fungal infections claim over two million lives annually, a problem exacerbated by rising resistance to current antifungal treatments and an increasing population of immunocompromised individuals. Despite this, antifungal drug development has stagnated, with few novel agents and fewer novel targets explored in recent decades. Here, we validate acetolactate synthase (ALS), an enzyme critical for branched-chain amino acid biosynthesis and absent in humans, as a promising target for new therapeutics. Using resistance gene-guided genome mining, we discovered a biosynthetic gene cluster BGC in Aspergillus terreus encoding HB-35018 (1), a novel spiro-cis-decalin tetramic acid that potently inhibits ALS. Biochemical and antifungal assays demonstrate that 1 surpasses existing ALS inhibitors in efficacy against Aspergillus fumigatus and other pathogenic fungi. Structural studies via cryo-electron microscopy reveal a unique covalent binding interaction between compound 1 and ALS, distinct from known inhibitors, and finally, we demonstrate that ALS is essential for virulence in a mouse model of invasive aspergillosis. These findings position ALS as a promising target for antifungal development and demonstrate the potential of resistance gene-guided genome mining for antifungal discovery.
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mhryu@live.com
February 1, 1:02 PM
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Glycosyltransferases (GTs) catalyze the formation of new glycosidic bonds and thus are vital for synthesizing nature's vast repertoire of glycans and glycoconjugates and for engineering glycan-related medicines and materials. However, obtaining detailed structural and functional insights for the >750,000 known GTs is limited by difficulties associated with their efficient recombinant expression. Members of the GT-C fold, in particular, pose the most significant expression challenges due to the integration and folding requirements of their multiple membrane-spanning regions. Here, we address this challenge by engineering water-soluble variants of an archetypal GT-C fold enzyme, namely the oligosaccharyltransferase PglB from Campylobacter jejuni (CjPglB), which possesses 13 hydrophobic transmembrane helices. To render CjPglB water-soluble, we leveraged two advanced protein engineering methods: one that is universal called SIMPLEx (solubilization of IMPs with high levels of expression) and the other that is custom tailored called WRAPs (water-soluble RFdiffused amphipathic proteins). Each approach was able to transform CjPglB into a water-soluble enzyme that could be readily expressed in the cytoplasm of E. coli cells at yields in the 3-6 mg/L range. Importantly, solubilization was achieved without the need for detergents and with retention of catalytic function. Collectively, our findings demonstrate that both SIMPLEx and WRAPs are promising platforms for advancing the molecular characterization of even the most structurally complex GTs, while also enabling broader GT-mediated glycosylation capabilities within synthetic glycobiology applications.
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mhryu@live.com
February 1, 11:08 AM
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Static structural models often fail to capture the dynamic mechanisms of protein interactions. To address this, we introduce DynaPIN, an open-source pipeline for extracting dynamic interface fingerprints from molecular simulations. DynaPIN unifies quality control metrics, interface prediction accuracy assessment, and atomistic interaction analysis into a single automated workflow, accessible at https://github.com/CSB-KaracaLab/DynaPIN A key feature is our interface-specific analysis centered on a Dynamic Interface definition, which classifies residues based on the persistence of their interaction status over the simulation. We applied DynaPIN to representative rigid, medium, and difficult targets from the DynaBench dataset, an MD simulation resource for Docking Benchmark 5.5. Our results show that interface flexibility diverges from static accuracy classifications established in Docking Benchmark 5.5, as explored before. All in all, by providing standardized, frame-resolved outputs, DynaPINs aim is to facilitate mechanistic studies and generate standardized unbiased data for future dynamics-aware artificial intelligence models.
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mhryu@live.com
February 1, 10:51 AM
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Microorganisms colonize all environments on Earth, yet it remains unclear which taxa merely broadly persist and which consistently outperform others across environments. Here we introduce the Baas-Becking score (BB-score), a performance metric to rank taxa across communities that integrates occupancy, relative abundance, and penalized absences. Applying BB-scores to 576,531 microbial communities spanning 24 biomes (categorized as either host-associated or free-living), we found that most species-level operational taxonomic units (OTUs) were widespread, but their success was substantially more restricted. Although 64% of OTUs were detected in at least one host-associated and one free-living biome, only six taxa ranked within the top 1% of performers in >50% of biomes: Aerococcus viridans, Faucicola (previously: Moraxella) osloensis, Lawsonella clevelandensis, Methylorubrum populi, Sphingobium yanoikuyae, and Pseudomonas fluorescens complex. These globally successful taxa were present in a quarter of all airborne communities, consistent with the atmosphere acting as a dispersal corridor. Network analysis of shared top 5% performers identified the phyllosphere and freshwaters as hubs linking animal-associated, plant-associated, and soil biomes. BB-score provides a scalable framework to map microbial success across Earth's biomes and to put new focus on globally successful yet woefully understudied taxa.
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Scooped by
mhryu@live.com
February 1, 10:39 AM
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Cells regulate processes through protein interaction networks. Most chemically induced dimerization (CID) systems respond to exogenous molecules, limiting integration with endogenous signaling. Here, we repurpose nuclear receptor (NR) ligand-binding domains (LBDs) and coactivators to develop hormone- or clinically approved drug-responsive CIDs. Using the LBDs of TRβ, VDR, RARγ, ERβ, and GR2 with a TIF2 coactivator peptide, we constructed CIDs responsive to triiodothyronine, vitamin D, retinoic acid, estrogen, cortisol, and their antagonists. These CIDs enable two-input transcriptional switches for gene regulation. Furthermore, we design hormone-responsive liquid-liquid phase-separated (LLPS) condensates that strongly amplify transcription when exceeding a critical interaction threshold. These functional LLPS condensates provide a tunable platform for transcriptional control with up to several hundred-fold activation. Our findings offer an approach for integrating synthetic biology with physiological signaling, advancing applications in gene circuits, biosensing, and therapeutics through ligand-controlled LLPS formation. Two-input chemogenetic tools remain limited. Here, authors develop ligand-responsive systems based on human nuclear receptors, using agonists and antagonists to reversibly control protein interactions and cellular processes, including synthetic protein condensate formation to enhance transcription.
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Scooped by
mhryu@live.com
January 31, 4:35 PM
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Expanding human space exploration necessitates technologies for sustainable local resource acquisition, to overcome unviable resupply missions. Asteroids, some of which rich in metals like platinum group elements, are promising targets. The BioAsteroid experiment aboard the International Space Station tested the use of microorganisms (bacteria and fungi) to extract 44 elements from L-chondrite asteroidal material under microgravity. Penicillium simplicissimum enhanced the release of palladium, platinum and other elements in microgravity, compared to non-biological leaching. For many elements, non-biological leaching was more effective in microgravity than on Earth, while bioleaching remained stable. Metabolomic analysis revealed distinct changes in microbial metabolism in space, particularly for P. simplicissimum, with increased production of carboxylic acids, and molecules of potential biomining or pharmaceutical interest in microgravity. These results demonstrate the impact of microgravity on bioleaching, highlighting the need for optimal combination of microorganisms, rock substrate, and conditions for successful biomining, in space and Earth.
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Scooped by
mhryu@live.com
January 31, 4:13 PM
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Temperate phages integrate multiple information sources to regulate lysis-lysogeny transitions. SPbeta-like phages use arbitrium signaling and DNA damage to control repressor activity during lytic induction, but how the repressor functions and is inactivated by the SOS response remains unclear. Here, we show that SroF, the SPbeta-like phage repressor, binds DNA via a mechanism involving its integrase-like fold, enabling stable prophage repression. Upon DNA damage, the host SOS response triggers derepression of an antirepressor, Sar. Sar binds SroF by mimicking the DNA structure recognized by the repressor, thereby inactivating its function and inducing phage. This mechanism is conserved across SPbeta-like phages, which encode multiple, specific SroF-Sar pairs. Surprisingly, repressor inactivation alone is insufficient for efficient induction when arbitrium levels are high. Our results uncover the mechanism underlying a double layer of control that ensures phage induction occurs only under SOS conditions and in the absence of neighboring prophages.
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mhryu@live.com
January 31, 3:46 PM
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Urinary tract infections (UTIs) are predominantly caused by uropathogenic E. coli (UPEC) and occur via an ascending route. UPEC invades bladder epithelial cells, causing cystitis and ascends to the kidneys, inducing pyelonephritis. Flagella-mediated motility is critical for this dissemination. The fliLMNOPQR operon encodes essential flagellar components, which are required for flagellar motility. However, the regulatory mechanisms that activate the expression of flagellar genes, facilitating bacterial motility in response to host cues, remain unclear. This study reported that the two-component system TCS HprSR directly activates fliLMNOPQR expression, promoting UPEC kidney colonization in response to host-derived reactive oxygen species (ROS) and reactive chlorine species (RCS). The hprSR mutation impairs UPEC kidney colonization due to reduced expression of flagellar genes. Neutralization of ROS and RCS in the mouse urinary tract prevents kidney colonization by inactivating HprSR. This study reveals a regulatory pathway in which host-derived signals activate UPEC virulence to mediate kidney colonization.
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mhryu@live.com
January 31, 3:26 PM
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Transposable element (TE) variants, the presence or absence of TE sequences such as LINE-1, Alu, SVA, and endogenous retroviruses, are a major source of genomic diversity and play critical roles in human health, evolution, and disease. As interest in TE variants grows, developing related methods and tools for detection has become increasingly important. However, rigorous benchmarking of TE variant detection methods remains limited due to the lack of accurate and scalable TE variant simulation platforms and the absence of reliable ground truth data. Here, we developed TEvarSim, a novel TE variant simulator that generates TE-containing genomic data in multiple formats, including genomes, short- and long-read sequencing data, and VCF files. TEvarSim supports both random and real-world TE insertions and deletions, including variants derived from pangenome graphs. It can rapidly simulate hundreds to thousands of synthetic chromosomes or genomes and model natural variation at the haplotype, individual, and population levels, making it well suited for large-scale studies. In addition, TEvarSim can directly compare simulated VCF files with TEs reported by TE detection tools, streamlining the benchmarking of TE genotyping methods. TEvarSim provides an all-in-one toolkit for simulating, evaluating, and improving TE variant detection, advancing our ability to accurately study TEs in health and disease in various species.
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mhryu@live.com
January 31, 3:16 PM
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Microalgae, a diverse assemblage of oxygen-generating photosynthetic organisms, demonstrate autotrophic, mixotrophic, and heterotrophic metabolic modes, facilitating adaptive regulation of their activity under different culture conditions and providing extensive biotechnological potential. Recently, there has been a growing interest in the cultivation of microalgae as biofilms owing to their potential for efficient biomass generation in confined systems and a wide range of industrial applications. This review offers a comprehensive overview of microalgal biofilm development, emphasizing adhesion mechanisms, variations in biofilm structure across diverse substrates, and the impact of critical physical parameters including cell density, size, morphology, and surface charge. Furthermore, the review examines the incorporation of different methods to attain a comprehensive understanding of biofilm development and molecular behavior while preserving biofilm integrity. The discussion encompasses the present challenges and future prospects of microalgal biofilms as biosensor components, highlighting their applications in environmental monitoring, on-chip biosensing, and biohybrid devices. The intrinsic benefits of microalgae, such as their capacity for self-regeneration, metabolic adaptability, and compatibility with optical and electronic systems, establish them as plausible candidates for sustainable biotechnological progress. By integrating mechanistic understanding, experimental methodologies, and application-focused approaches, this review seeks to establish a comprehensive framework for the advancement of next-generation microalgal biofilm technologies.
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mhryu@live.com
January 31, 2:57 PM
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The role of gut microbiome in predicting diet response and developing personalized dietary recommendations has been increasingly recognized. Yet, we still lack comprehensive, genome-based insights into which gut microbes metabolize specific dietary compounds. Here, we leveraged the metabolic networks constructed from well-annotated microbial genomes to characterize the potential interactions between microbes and metabolites, specifically emphasizing the interactions between microbes and dietary compounds. We revealed a substantial, approximately fourfold variation in both the number of metabolites and dietary compounds in the microbial genome-scale metabolic networks across different genera, whereas species within the same genus showed a high metabolic similarity (mean coefficient of variation in microbial network degree CV = 0.023 for metabolites and 0.015 for dietary compounds). We found that the number of species that can utilize a metabolite drastically varies, ranging from 1 to 818 species, with some metabolites being used by a wide range of species (211 out of 1390 metabolites used by more than 95% of species) and others only by a few species (435 metabolites used by less than 5% of species). Leveraging a longitudinal microbiome study, we observed that microbial taxa with similar metabolic capacity tend to have positively correlated abundances, and the gut microbiome’s capacity to process dietary compounds is functionally stable. Finally, we propose a network-based method to identify the dietary compounds that are specific to no more than 10 microbial species, offering a new strategy for combining a dietary compound and its linked microbial species to design synbiotics. Our results quantitatively reveal large-scale variation and redundancy in gut microbial metabolism and identify dietary compounds linked to only a few microbial species. These findings improve understanding of microbe-metabolite interactions and provide a foundation for the rational design of microbiome-based interventions for healthy benefits.
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mhryu@live.com
January 31, 2:10 PM
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Bacteriophages, viruses that infect bacteria, are critical players for shaping the taxonomic and functional composition of plant-associated microbiomes. Yet, their roles in plant health remain overlooked, along with their implications for sustainable agriculture. While phages are recognized as bacterial predators, they can also promote bacterial survival and competitiveness. Here, we highlight the roles phage play in shaping soil microbiomes and promising phage-based applications for sustainable agriculture. Ongoing research highlights the diverse roles of phages in regulating bacterial populations, enhancing nutrient cycling, improving stress tolerance, and suppressing soil-borne pathogens – microbial traits that directly link to plant health. Additionally, emerging applications such as bioremediation, phage-based biosensors, and microbiome engineering underscore phages' potential to revolutionize sustainable farming and optimize agricultural productivity.
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Scooped by
mhryu@live.com
February 1, 1:33 PM
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Genetic manipulation of core gut probiotics remains challenging due to endogenous cellular barriers and a scarcity of efficient molecular tools, limiting progress in live biotherapeutic development. Here, we characterized the native type II-C CRISPR-Cas system in Bifidobacterium longum subsp. longum GNB (B. longum GNB). Through integrated bioinformatic analysis and high-throughput protospacer adjacent motif (PAM) screening, we identified a novel 5′-NNRMAT-3′ (where R = A/G, M = A/C) motif recognized by its compact Cas9 nuclease (BLCas9). The stringent PAM dependency of BLCas9 was unequivocally confirmed by in vitro cleavage assays. Leveraging this endogenous mechanism, we developed a dual-plasmid editing platform for robust and multiplex genome engineering in the probiotic strain E. coli Nissle 1917. Application of this system notably enhanced extracellular γ-aminobutyric acid (GABA) production in EcN through targeted metabolic engineering. Our work provides the first molecular dissection of a type II-C system in Bifidobacterium longum and establishes a generalizable framework for the discovery and application of compact programmable nucleases, suggesting a viable strategy for modulating host physiology via the gut-brain axis.
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Scooped by
mhryu@live.com
February 1, 1:08 PM
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Cyclic dinucleotide (CDN) signaling molecules, such as cyclic di-GMP (c-di-GMP) and 3',3' cyclic GMP-AMP (cGAMP), are second messengers that play critical roles in phenotypic regulation, such as biofilm formation, host colonization, and bacterial virulence. Recently, hybrid promiscuous (Hypr) GGDEF proteins have been identified in certain bacteria to produce both cyclic dinucleotides. One such enzyme, Bd0367, from the predatory Bdellovibrio bacteriovorus, switches between synthesizing c-di-GMP and cGAMP to regulate the bacterial predation cycle and prey exit. However, the molecular mechanism controlling this switch remains unknown. Here, we introduce an RNA-based ratiometric, dual metabolite biosensor that enables simultaneous detection of c-di-GMP and cGAMP in live cells. This sensor integrates a Pepper-based biosensor for c-di-GMP detection and a Spinach2-based biosensor for cGAMP detection into a single transcript, producing distinct fluorescent outputs. In E. coli, the dual metabolite sensor reliably reported shifts in c-di-GMP/cGAMP production ratios from various CDN synthases, including Bd0367. Additionally, a histidine kinase was discovered as the probable regulatory partner of Bd0367. These findings demonstrate the sensor's capacity to assess relative CDN levels and to uncover complex signaling pathways. Together, this ratiometric dual metabolite biosensor provides a foundation for broader applications of fluorogenic RNA biosensors in dissecting bacterial signaling networks, microbial ecology, and host-pathogen interactions.
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Scooped by
mhryu@live.com
February 1, 11:11 AM
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Protein-ligand binding site prediction (LBS) is important for many domains including computational drug discovery, where, as in other tasks, protein language models (pLMs) have shown a great promise. In their application to LBS, the pLM classifies each amino acid as binding or not. Subsequently, for the purposes of downstream analysis, these predictions are mapped onto the structure, forming structure-continuous pockets. However, their residue-oriented nature often results in spatially fragmented predictions. We present a comprehensive framework (Seq2Pocket) that addresses this by combining finetuned pLM with an embedding-supported smoothing classifier and an optimized clustering strategy. While finetuning on our enhanced scPDB dataset yields state-of-the-art results, outperforming existing predictors by up to 11\% in DCC recall, the smoothing classifier restores pocket continuity. Next, we introduce the Pocket Fragmentation Index (PFI) and use it to select a clustering approach that preserves a consistent mapping between predictions and ground-truth pockets. Validated on the LIGYSIS and CryptoBench benchmarks, our approach ensures that pLM-based predictions are not only statistically accurate but also useful for downstream drug discovery, while maintaining state-of-the-art performance.
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Scooped by
mhryu@live.com
February 1, 10:58 AM
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Alternative splicing expands proteomic diversity and is shaped by interactions between RNA‑binding proteins (RBPs) and multivalent RNA motifs. Linking sequence elements to regulatory proteins remains difficult from sequence information alone. Here we present RNAMaRs, a interpretable statistical framework that combines motif discovery with in vivo binding and splicing responses to infer motif-RBP relationships. RNAMaRs learns RBP binding principles, weights signal quality, and optimizes motif discovery in an RBP-specific manner. Across ENCODE datasets RNAMaRs consistently prioritizes the perturbed regulator, especially for large splicing effects. Independent validation in prostate cancer cells recapitulates HNRNPK binding signatures, supporting transferability across an unseen cellular context.
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Scooped by
mhryu@live.com
February 1, 10:46 AM
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Antibiotics are known to induce new persister cells during treatment, yet the inability to distinguish and quantify pre-existing versus drug-induced persisters has long obscured how antibiotics and genes shape persistence. Here, we develop a quantitative framework integrating kinetic modeling with serial-dilution time-kill (SDTK) assays to resolve persister population dynamics and accurately quantify both persister types. We show that antibiotic exposure dynamically generates a substantial number of persisters that are heterogeneous and distributed along a persistence spectrum. Across antibiotics, we uncover pronounced differences in rates of persister induction and elimination, with ampicillin inducing persisters at the highest rate and kanamycin at the lowest. Depending on dilution history, drug-induced persisters can dominate the persister pool. Our framework enables identification of genetic determinants specific to pre-existing and/or drug-induced persistence and reveals drug-dependent pre-existing persister fractions. Systematic sequential-drug treatments demonstrate that kanamycin persisters form the most tolerant subset, embedded within ciprofloxacin persisters that in turn are nested within the broader ampicillin persister subpopulation. Together, we propose a Drug-Induced Persistence-Spectrum (DIPS) model in which antibiotics differentially induce and select for persister subsets along a tolerance continuum.
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Scooped by
mhryu@live.com
February 1, 10:27 AM
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Quorum sensing (QS) orchestrates collective microbial behaviors and functional acclimatization through chemical communication. However, QS in natural waters is challenged by dilution, alkaline hydrolysis, and enzymatic degradation of freely dissolved autoinducers. Here, we demonstrate that extracellular vesicles (EVs) act as selective, durable, and protective vectors for QS signal molecules under environmental stresses. Specifically, EVs preferentially package hydrophobic acyl‑homoserine lactones, concentrate them locally, and shield them from alkaline hydrolysis, and exhibiting long-distance transport. In addition, EVs possess specific affinity to recipients, thus influencing microbial community. Field investigation via multi-omics showed that EV abundance covaried with salinity, nutrients, chlorophyll a, and biomass, which were validated by culture experiments. Our statistical framework demonstrated that organisms producing moderate EV levels contributed significantly to maintaining community stability and ecosystem functions. Distinctively within this group, QS-active species (including Burkholderiaceae, Pseudomonadaceae, Rhodobacteraceae, Roseobacteraceae, Flavobacteriaceae etc.) emerge as key drivers facilitating these crucial ecological roles. Furthermore, metaproteomics of field EVs reveal QS receptor and synthesis proteins, suggesting coordinated transport of signals and proteins, which indicate new routes for QS crosstalk, particularly for taxa bearing luxR/I solos. Our results show that moderately generated EVs are the potentially important QS signal carriers and ecological regulation hubs in natural waters.
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Scooped by
mhryu@live.com
January 31, 4:25 PM
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Many temperate Bacillus phages use the arbitrium peptide-based signaling system to regulate lysis-lysogeny decisions. In this system, the secreted AimP peptide inhibits the AimR receptor to promote lysogeny. However, the downstream mechanism of AimR-mediated lysis control remains unclear for most systems. Here, we identify that ∼75% of arbitrium systems possess an extended five-gene module, including the aimX, aimC, and aimL genes. AimX encodes a small AimR-regulated antirepressor protein that binds the phage repressor AimC, preventing its oligomerization and DNA binding, thereby activating the pro-lytic aimL gene and additional lytic genes. This mechanism was validated across multiple phages and structurally characterized, revealing that AimX mimics the AimC oligomerization domain to prevent oligomerization and inhibit repressor function. These findings elucidate the predominant molecular strategy by which arbitrium systems control phage lysis-lysogeny transitions and highlight the central role of small proteins in phage decision-making.
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mhryu@live.com
January 31, 3:54 PM
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The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-phage immune systems that confer resistance to therapeutic phages. Chemical inhibitors of these antiphage immune systems could be employed as adjuvants to overcome resistance in phage-based therapies. Here, we report a class of chemical inhibitors that selectively inhibit type II Thoeris anti-phage immune systems from diverse bacteria—including antibiotic-resistant pathogens, thereby sensitizing phage-resistant bacteria to phages. These inhibitors block the biosynthesis of a histidine-ADPR intracellular “alarm” signal by ThsB, thereby preventing ThsA from arresting phage replication. Chemical inhibition of the Thoeris defense improves the efficacy of a model phage therapy against a phage-resistant clinical isolate of P. aeruginosa in a mouse infection, suggesting a therapeutic potential. These findings demonstrate that the selective inhibition of anti-phage defense systems can improve the efficacy of therapeutic phages, suggesting a strategy to circumvent phage-therapy resistance.
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mhryu@live.com
January 31, 3:42 PM
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The coevolution of plant-microbe (PM) associations over approximately 450 million years has been a fundamental driver of terrestrial life, giving rise to mutualistic, commensal, and pathogenic relationships along a dynamic friend-foe continuum. The need to adapt to the host environment has driven the convergent evolution of common strategies among mutualists and pathogens, enabling them to evade or modulate the plant immune system. This review synthesizes PM coevolution within a deep-time, three-pillar framework: organellogenesis, root evolution, and immune gatekeeping, linking ancient endosymbiotic events (mitochondria, chloroplast, and nitroplast) to contemporary holobiont-level phenotypes and biotechnological applications. We organize the friend-foe continuum around a coevolution-guided cost-benefit and tipping-point framework, using identified molecular switches and evolutionary constraints to derive actionable design rules for engineering PM associations. Moving beyond a descriptive toolbox of technologies, we integrate recent breakthroughs to analyze how four principal axes: host and microbial genetics, evolutionary dynamics, environmental and ecological conditions, and metabolic switches define the thresholds that govern microbial lifestyle transitions. Finally, we propose specific, testable strategies for PM coevolution-informed crop improvement, distinguishing near-term feasible targets from long-term speculative goals in nitrogen utilization, synthetic microbial communities, immune receptor engineering, modulation of plant memory, and microbiome-integrated breeding through genome editing, synthetic biology, AI, and microbiome engineering. Together, these approaches extend existing syntheses into a predictive, evolution-informed framework that transforms coevolutionary principles into a functional blueprint for sustainable and resilient agriculture.
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Scooped by
mhryu@live.com
January 31, 3:22 PM
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Microbes regulate their dynamic behaviors using the chemical and physical characteristics of their environment. The ability of microbes to continuously convert this physicochemical information into biochemical information and to use organic matter in the environment as a power source makes these organisms attractive as chassis for building sensors. However, most biosensors have severe limitations when considering applications in hard-to-image settings like soils, sediments, and wastewater. Emerging technologies at the interface of biomolecular design, microbiome engineering, and synthetic biology offer new tools to program cells and communities as biosensors for these settings. In this review, we describe innovations in biosensor outputs that are enabling new applications in complex environments, including reporters that are read out using electrochemical, gas chromatography, hyperspectral imaging, and next-generation sequencing methods. We also discuss computational advances that are accelerating the diversification of sensing components by mining metagenomics data for new transcriptional regulators and by designing allosteric protein switches that directly regulate reporter outputs using analytes. We highlight emerging opportunities for programming undomesticated microbes in communities to function as distributed sensors in the environment. Finally, we discuss the need for responsible biosensor development and to modernize regulatory frameworks to support evidence-based assessment of environmental biosensors.
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Scooped by
mhryu@live.com
January 31, 3:07 PM
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Introns are generally considered rare in bacteria, yet they are frequently observed in Patescibacteria, which have highly reduced genomes. To systematically explore the diversity, roles, and evolution of introns in Patescibacteria, we first focused on the tRNA introns. Using 95 complete genomes, we identified tRNAAsn and tRNAAsp genes previously undetected by standard annotation tools due to group I introns inserted at an unusual position, 35/36, in the anticodon loop. In vitro splicing assays confirmed that these introns catalyze precise self-splicing, validating our computational approach. A large-scale survey of complete bacterial genomes revealed that intron insertions at position 35/36 are highly enriched in Patescibacteria but rare in other phyla. Subgroup classification indicated that 81% of all tRNA introns belong to the IC subgroup, whereas nearly all Patescibacteria introns were classified as IA. As most tRNA introns lack homing endonuclease genes, horizontal transfer appears limited. Comparative analysis across bacterial phyla showed that Patescibacteria and Cyanobacteriota exhibit the highest prevalence of group I introns (~40% of genomes). In contrast, group II introns, which require protein cofactors for activity, were more common in other bacteria, including Cyanobacteriota, but absent in Patescibacteria. Collectively, these findings suggest that Patescibacteria harbor introns with phylum-specific trends in abundance, structure, and evolutionary lineage. The coexistence of extensive genome reduction and persistent group I introns may reflect an adaptive strategy, where introns serve as efficient RNA-based regulatory elements, potentially substituting for complex protein-mediated systems.
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Scooped by
mhryu@live.com
January 31, 2:46 PM
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Microorganisms in groundwater ecosystems exist either as planktonic cells or as attached communities on aquifer rock surfaces. Attached cells outnumber planktonic ones by at least three orders of magnitude, suggesting a critical role in aquifer ecosystem function. However, particularly in consolidated carbonate aquifers, where research has predominantly focused on planktonic microbes, the metabolic potential and ecological roles of attached communities remain poorly understood. To investigate the differences between attached and planktonic communities, we sampled the attached microbiome from passive samplers filled with crushed carbonate rock exposed to oxic and anoxic groundwater in the Hainich Critical Zone Exploratory and compared it to a previously published, extensive dataset of planktonic communities from the same aquifer ecosystem. Microbial lifestyle (attached vs. planktonic) explained more variance in community composition than redox conditions, prompting us to further investigate its role in shaping functional and activity profiles. Metagenomic analysis revealed a striking taxonomic and functional segregation: the 605 metagenome-assembled genomes (MAGs) from attached communities were dominated by Proteobacteria (358 MAGs) and were enriched in genes for biofilm formation, chemolithoautotrophy, and redox cycling (e.g., iron and sulfur metabolism). In contrast, the 891 MAGs from planktonic communities were dominated by Cand. Patescibacteria (464 MAGs) and Nitrospirota (60 MAGs) and showed lower functional versatility. Only a few genera were shared, and even closely related MAGs (> 90% average nucleotide identity) differed in assembly size and metabolic traits, demonstrating lifestyle-specific functional adaptation. Analysis of active replication indicated that the active fraction of the attached community was primarily represented by the most abundant MAGs. Planktonic communities featured a higher fraction of active MAGs compared to attached communities, but overall with lower relative abundances. The high abundance, metabolic specialization, and carbon fixation potential of attached microbes suggest that they are key drivers of subsurface biogeochemical processes. Carbonate aquifers may act as much larger inorganic carbon sinks than previously estimated based on CO2 fixation rates of the planktonic communities alone. Our findings underscore the need to incorporate attached microbial communities into models of subsurface ecosystem function.
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genome editing