Many antiphage defence systems directly bind a specific phage-encoded protein that acts similar to a pathogen-associated molecular pattern to activate an immune response. Such activation is often assumed to occur independent of host factors. Here we demonstrate that the antiphage defence protein CapRelEbc, a fused toxin–antitoxin system from Enterobacter chengduensis, senses the T7 phage-encoded protein Gp0.4 in complex with the host bacterial factor FtsZ, an essential cell division protein. During T7 infection, Gp0.4 sequesters monomeric FtsZ to block its polymerization and thereby inhibit bacterial cell division. Only the complex of Gp0.4–FtsZ, but neither protein alone, triggers CapRelEbc activity. Structural modelling and hydrogen–deuterium exchange mass spectrometry indicate that Gp0.4, FtsZ and CapRelEbc form a ternary complex that activates phage defence. Our work suggests that activation of bacterial immune systems does not always depend exclusively on phage-encoded triggers. Instead, activation can involve host factors targeted by phages, analogous to how eukaryotic innate immune systems detect pathogen-induced perturbations of host cells through effector-triggered immunity. The activation of an antiphage defence system relies on host factors targeted by phages, a mechanism analogous to the way that eukaryotic innate immune systems detect pathogen-induced perturbations of host cells through effector-triggered immunity.

Anaerobic treatment of industrial wastewater offers a sustainable and cost-effective approach to reducing environmental contamination while recovering biogas. High-salinity wastewater poses ecological risks and remains difficult to treat due to salt-induced sludge disintegration, volatile fatty acid accumulation, and reduced methane production. Quorum sensing is emerging as a key regulator of microbial activity and system stability under salt stress. This review summarizes salinity-stress inhibition mechanisms, evaluates quorum sensing-based mitigation strategies, and proposes a stage- and performance-based framework for quorum sensing application to advance resilient and efficient anaerobic treatment systems.

Bacteria–phage coevolution often results in correlated fitness effects on partner species. Whether coevolutionary changes impact the ecology of the surrounding communities is unclear. Here we link coevolution between the phytopathogenic bacterium Ralstonia pseudosolanacearum and its phage parasites to bacterial wilt disease patterns across four geographically disconnected tomato fields. We find that bacteria and phages are locally adapted between and within fields. Phage infectivity was highest on sympatric bacteria, and bacteria showed greater phage resistance when isolated from healthy than diseased plants. The modularity of phage–bacteria coevolution was associated with field-specific anti-phage defence system patterns and locally adapted phage populations. Moreover, phages selected for field-specific mutations in different phage receptor genes, which were negatively associated with virulence measured in planta, suggesting why phage-resistant but weakly virulent pathogen isolates are associated with healthy tomato plants within fields. Our findings show that bacteria–phage coevolution results in patchy plant disease distribution through phage resistance–virulence trade-offs. Phage–bacteria coevolution is associated with field-specific anti-phage defence and locally adapted phage populations, resulting in phage-resistant but weakly virulent pathogens.

Understanding how nutrient-specific limitations shape anaerobic metabolism in Saccharomyces cerevisiae is essential for defining the physiological limits of yeast growth. Integrating chemostat physiology, multi-omic profiling, and targeted metabolic engineering under strictly anaerobic conditions, we show that yeast maintains a conserved maximum glucose uptake (~14 mmol/gDW/h) under carbon (C), nitrogen (N), and phosphorus (P) limitation, while distinct regulatory bottlenecks constrain maximal growth rate: ATP insufficiency under C and P limitation, and aminoacyl-tRNA synthetase scarcity under N limitation. Under these stresses, S. cerevisiae reallocates proteomic resources toward anabolic functions, with nutrient-specific phosphorylation networks compensating for translational stress, most pronounced under N limitation. Building on these insights, a “push–pull” strategy enhancing energy supply (VMA3) and translational capacity (WRS1) increased the maximal anaerobic growth rate by 27.2%, 47.5% and 52.5% under C, N, and P limitation, respectively. These findings reveal energy–translation coupling as the central determinant of anaerobic growth limits and provide a framework for rational strain engineering. Saccharomyces cerevisiae must balance limited protein resources between energy generation and translation capacity. Here, authors map these trade-offs in yeast under nutrient stress, revealing a coupled energy-translation bottleneck that can be engineered to synergistically boost anaerobic growth and ethanol yields.

Ribosomes are central to protein synthesis but also serve as dynamic hubs that integrate cellular stress responses. Here, we investigate how ribosomal protein L11 regulates ribosome conformational dynamics and long-distance coupling. Long-timescale molecular dynamics simulations of wild-type and L11-deleted (ΔL11) ribosomes reveal that L11 functions as a global allosteric regulator coordinating communication between the ribosomal stalk and the peptidyl transferase center. The absence of L11 disrupts long-distance couplings involving RelA and Obg and rigidifies the hibernation-promoting factor site, suggesting altered hibernation dynamics that could affect ribosome persistence under stress. To examine the physiological implications of these computational predictions, we construct a ΔL11 Bacillus subtilis strain and quantify its sporulation behavior. The ΔL11 variant exhibits delayed entry into and exit from dormancy, consistent with a breakdown in stress-adaptive ribosomal regulation. Overall, these results highlight the role of L11 in ribosomal allostery, suggesting how local perturbations propagate through the ribosome to influence global physiological outcomes and bacterial survival under environmental stress. Ribosomes are crucial for protein synthesis and managing cellular stress. Here, authors show that ribosomal protein L11 acts as a global regulator, coordinating complex internal signaling to ensure proper bacterial survival during environmental stress.

Probiotic supplements are marketed for diverse health benefits, yet species inclusion often lacks functional rationale. Our survey of 352 over-the-counter probiotic products available in the USA revealed 36 unique microbial species. However, there is no clear link between species inclusion and the intended health benefit. Here, to address this gap, we developed HaPaPro, a collection of 1,012 genome-scale metabolic models spanning pathogenic, probiotic and host-associated bacteria, constructed from publicly available genome sequences. Flux balance analysis revealed that probiotic species fail to capture the metabolic diversity of host-associated microbes. Focusing on vaginal health, we computationally identified vaginal microbes with metabolic profiles overlapping Gardnerella vaginalis. In vitro spent media assays using 11 vaginal isolates showed variable inhibition of G. vaginalis, primarily driven by d-lactic acid production, which was also produced by non-Lactobacillus species. These findings highlight the need for function-based probiotic design and demonstrate a scalable framework integrating metabolic modelling with experimental validation. Metabolic modelling and experimental validation reveal that current probiotics lack the functional diversity of native microbes, identifying vaginal species that inhibit Gardnerella vaginalis through the dual mechanisms of resource competition and d-lactic acid production.

Global agricultural productivity is increasingly destabilized by climate change—driven droughts, floods, extreme heat, and severe storms. Although the climate-smart agriculture (CSA) framework addresses these challenges, implementation has focused mainly on plant genetics and agronomic inputs, leaving the adaptive potential of the crop microbiome underexplored. Here, we examine the agricultural use of synthetic microbial communities (SynComs) through the “crop holobiont” concept, in which plants and their associated microbiota function as an integrated, responsive system rather than through plant genomes alone. Pioneer plants in extreme environments may serve as reservoirs of stress-adapted microbes and provide a strategic toolkit for advancing CSA. SynComs assembled from these microbes can act not only as nutrient suppliers but also as dynamic physiological modulators that enhance crop phenotypic plasticity under climatic stress. We propose a roadmap for crop microbiology that integrates synthetic ecological engineering, with broad implications for CSA.

While the central dogma outlines DNA-to-protein information flow, existing gene regulators mainly target transcription. Here, we developed the λN-Guided RNA Targeting System (λGRTS), a CRISPR-independent platform enhancing mammalian mRNA translation via specific translation-guiding RNAs (tgRNAs). λGRTS integrates λN (high-affinity BoxB binder), mutated eIF4E1 (ablated non-specific 5′ cap binding, retains TIC recruitment), and auxiliary factors (HuR for dsRNA stabilization, PABP and RRM2-RRM3 for mRNA closed loops). Optimized 22-nt tgRNAs (targeting 58 bp upstream of mRNA ATG in 5′ UTR) and NES-tagged proteins maximized efficacy. λGRTS outperformed dCasRX (smaller ~ 50 kDa vs. ~ 150 kDa, single tgRNA vs. crRNA-tracrRNA), boosting functional proteins (e.g., GFP). It activated P53/PTEN, suppressing GBM cell proliferation, inducing G1 arrest, and reducing invasion in vitro. In vivo, lentiviral λGRTS inhibited orthotopic GBM in nude mice, extended survival by approximately 35–40 days, with IHC confirming P53/PTEN upregulation. Mass spectrometry showed no off-target effects. Cross-species tests (human, mouse, bovine cells) validated broad applicability via conserved eIF4E1. λGRTS offers a specific, safe translation-centric tool for gene regulation and oncology research.

Communication between bacteriophages, particularly in biofilms, has long been studied. The recent discovery of the arbitrium lysis-lysogeny switch in Bacillus phages, similar to bacterial quorum sensing, has renewed interest in phage communication. This review examines the arbitrium system alongside other switching mechanisms, explores its role in pathogen-phage-host immune interactions, and proposes design principles for “smart” phage therapies.

Ralstonia solanacearum is a major plant pathogen causing bacterial wilt, whose unpredictable onset hinders timely detection and effective control. Here, we report the design, preparation and field use of a dual pH-responsive multifunctional double network (DN) hydrogel for the efficient and sustainable control of bacterial wilt. The primary network of carboxylated agarose chelates Zn2+ and loosens under acidic conditions (pH ≤ 5) to release a pesticide (zhongshengmycin) and Zn2+, while the secondary L-phenylalanine (Phe)/ Zn2+ network disassembles to provide additional bioactive components (Phe and Zn2+). This dual-triggered release achieves a combined antibacterial effect, enhances plant growth, and activates plant disease resistance pathways. A simple root application protects plants for up to 14 days, and field experiments demonstrate disease control for up to 30 days, significantly preserving tomato yield. Here, we present a sustainable, effective system for managing bacterial wilt and highlight the potential of smart hydrogels in crop protection. Bacterial wilts unpredictable onset makes control difficult. Here, the authors report on a dual pH-responsive hydrogel system which releases antimicrobial agents and plant immune elicitors, L-phenylalanine and zinc, in acidic soils to enable control of bacterial wilt.

Formate is an exciting potential microbial feedstock as it can be derived from CO2 and electricity. Despite this, limited progress has been made in engineering formatotrophy in yeasts, and no yeasts grow using formate naturally. Here we use metabolic modelling to find two potential formatotrophy pathways in Yarrowia lipolytica. We then use C13 tracer analysis and computationally guided growth experiments to show that wild-type Y. lipolytica possesses strong formate dissimilation and a cyclical C1 pathway with similar architecture to the synthetic serine–threonine cycle, which it uses to co-assimilate formate and glycerol. RNA-seq shows that formate exposure results in increased oxidative stress and changes in the tricarboxylic acid cycle, redox and C1 metabolism. Following this, we use model-guided adaptive laboratory evolution to produce a formatotrophic strain of Y. lipolytica using the eukaryotic serine–threonine cycle. We then use further messenger RNA sequencing to show that formatotrophy is supported by changes in adenosine triphosphate and reactive oxygen species metabolism. Subsequently, we engineer nicotinamide adenine dinucleotide phosphate (NADPH) and reactive oxygen species metabolism to create a strain with substantially improved growth. This strain reaches about 10% of the theoretical maximum biomass yield, highlighting its potential for additional engineering approaches. Finally, we show that beta-carotene production from formate is possible in our engineered strain, opening the door to formatotrophic eukaryote bioprocesses. Yarrowia lipolytica is a non-model yeast of considerable industrial interest. Here metabolic modelling and directed evolution are used to create a strain of Y. lipolytica that is able to grow on formate as a step towards electrical CO2-based bioprocesses based on a complex metabolic pathway.