Search Results (283)

The Asian corn borer, Ostrinia furnacalis, is a major pest in China and across East and Southeast Asia, serving as the primary target of Bt maize expressing Cry proteins. Evolution of resistance to Bt toxins represents a critical challenge in plant protection. The high-dose/refuge strategy is more effective when resistance is recessively inherited and fitness costs are present. Here, we characterize the inheritance pattern and fitness costs of Cry1Ab resistance in O. furnacalis using a resistant strain exhibiting a resistance ratio of >1400-fold. The LC₅₀ values of F₁ hybrids from reciprocal crosses between resistant and susceptible strains were 2.44 (1.90–3.12) μg/g and 2.01 (1.53–2.61) μg/g, respectively, with no significant difference, indicating autosomal inheritance. The effective dominance (h) of F₁ offspring decreased with increasing concentration, suggesting that resistance was concentration-dependent. Analysis of observed versus expected mortality in backcross progeny (F₁ × resistant strain) indicated that Cry1Ab resistance is likely governed by more than one genetic locus. Compared with the susceptible strain, resistant individuals exhibited prolonged larval development (18.6 d vs. 17.2 d, p < 0.001), reduced pupation (42.5% vs. 60.8%, p < 0.001) and adult emergence rates (60.3% vs. 87.8%, p < 0.001), while fecundity was not significantly affected. These results verify the existence of fitness costs associated with Bt resistance. Our findings provide important insights into the mechanistic basis of Cry1Ab resistance and will assist in designing proactive management strategies to delay resistance evolution in field populations of O. furnacalis. Full article

Antibiotic resistance is a growing global health threat. However, its evolution cannot be fully understood without considering antibiotic tolerance and persistence. Persister cells are phenotypic variants that survive lethal antibiotic exposure without heritable resistance, primarily through growth arrest, metabolic slowdown, and stress-adaptive states. Although persistence has been viewed as a transient survival phenomenon, increasing evidence suggests that it may also have a genetic basis by preserving populations during antibiotic-induced bottlenecks and enabling regrowth, mutation, and selection under certain conditions. This review examines the molecular mechanisms underlying persister formation, including toxin–antitoxin systems, stringent-response signaling, ATP depletion, translational arrest, and stress-response networks. We discuss how persistence contributes to antibiotic tolerance in biofilms, host environments, and recurrent infections, and how repeated antibiotic exposure may promote stepwise evolution from phenotypic survival to stable resistance in specific contexts. Evidence from experimental evolution, clinical observations, and system-level analyses supports a potential but context-dependent link between persistence and resistance. We also highlight therapeutic strategies targeting persister cells, including antipersister compounds, metabolic activation, combination therapies, bacteriophages, and alternative approaches. Finally, we outline future research directions, emphasizing single-cell technologies, systems biology, longitudinal clinical studies, and evolution-informed treatment design. A comprehensive understanding of persistence and its evolutionary implications is essential for improving treatment efficacy and limiting the emergence of long-term antibiotic resistance. Full article

Heavy metals in the soil inhibit plant growth, which significantly reduce the crop yield and quality. Natural Resistance-Associated Macrophage Proteins (NRAMP) are widely distributed on the plasma and vacuolar membranes of plant roots, stems, and leaves. The NRAMP gene family plays a crucial role in modulating plant heavy-metal uptake, sequestration, distribution, and translocation, while the molecular evolution and mechanisms underlying these processes remain unclear. Here, we reviewed recent progress on plant NRAMP genes, focusing on their structural characteristics and functions in the absorption, transport, accumulation, and detoxification of various heavy metals. Furthermore, we performed an evolutionary analysis of NRAMP in green plants, indicating expansion and tandem duplication in ferns. In addition, their key amino acid sequences and secondary structures were highly conserved across plant species. The expression of diverse tissue showed that NRAMP genes displayed distinct spatial regulation in the leaves and roots. We also explored the underlying molecular mechanisms and regulatory pathways by which NRAMP genes influence heavy metal uptake. Therefore, by integrating structural conservation, molecular evolution, tissue- and single-cell expression patterns, ion-stress-responsive expression, regulatory pathways, and the Cd–Mn nutrient–toxin trade-off, this review provides a framework for identifying unresolved NRAMP functions and for guiding future strategies in low-heavy-metal crop breeding, metal homeostasis engineering, and phytoremediation. Full article

Salmonella persistence contributes to infection relapse, chronic carriage, and reduced antibiotic efficacy. Traditionally viewed as dormant subpopulations that passively survive antibiotic exposure, persister cells are now increasingly recognized as dynamic, heterogeneous, and context-dependent physiological states shaped by bacterial regulatory programs and host microenvironmental pressures. This review examines Salmonella persistence from a multiscale perspective. We first clarify key antibiotic survival phenotypes, including resistance, heteroresistance, tolerance, persistence, and viable but non-culturable states. We then discuss how host-derived stressors, such as phagosomal acidification, nutritional restriction, metal perturbation, and reactive oxygen and nitrogen species, promote growth-restricted, persistence-associated bacterial states. At the bacterial level, we summarize stress-response networks involving the stringent response, SOS response, toxin–antitoxin systems, and auxiliary regulators that coordinate metabolic remodeling, growth restriction, and antibiotic survival. At the host level, we highlight how organ reservoirs, immune cell subsets, metabolic cues, and Salmonella-mediated immune niche remodeling shape persistence-associated phenotypes in vivo. Finally, we discuss clinical and translational implications, including endogenous relapse, resistance evolution, and emerging anti-persistence strategies. Together, this review provides a framework for understanding Salmonella persistence as a multiscale, niche-dependent process relevant to recurrent and chronic infection. Full article

Background/objectives. Clostridioides difficile infection (CDI) remains a major cause of healthcare-associated infectious colitis, particularly among elderly and multimorbid patients. Disease severity and clinical evolution are influenced by the host’s systemic inflammatory response. This study aimed to evaluate the hematological and inflammatory profile of hospitalized CDI patients and to explore the prognostic value of routine laboratory parameters for prolonged hospitalization. Methods. A retrospective observational study was conducted on 50 adult patients hospitalized with laboratory-confirmed CDI (positive glutamate dehydrogenase, antigen and toxins A/B). Hematological parameters (WBC, hemoglobin, RDW) and inflammatory markers (CRP, fibrinogen) were analyzed at admission and discharge. Prolonged hospitalization was defined as length of stay (LOS) > 8 days (cohort median). Multivariable logistic regression was performed to assess admission predictors of prolonged hospitalization, and model discrimination was evaluated using leave-one-out cross-validation (LOOCV). Results. At admission, patients exhibited marked inflammatory activation accompanied by reduced hemoglobin and elevated RDW. Significant correlations were observed between inflammatory markers. All inflammatory and hematologic parameters improved at discharge. In multivariable analysis, lower admission hemoglobin and higher log-transformed CRP showed exploratory associations with prolonged hospitalization. The internally validated model demonstrated moderate discriminative performance (AUC = 0.65). Conclusions. CDI is associated with substantial systemic inflammatory activation and hematologic alterations. While no individual predictor reached statistical significance, the observed effect sizes provide hypothesis-generating estimates to inform future prospective validation studies. Full article

Rhabdophis lateralis is a snake species within the family Natricidae, which is widely distributed across mainland China, Russia, and Korea. Although this species was once thought to be non-venomous, there are quite a few cases demonstrating its bite could be fatal. In this study, we performed de novo assembly and analysis of the transcriptome data from the Duvernoy’s gland of R. lateralis, aiming to characterize its venom transcriptome and reveal the molecular basis of its toxicity. Among 6196 annotated transcripts, 77 were identified as potential toxin transcripts belonging to 26 toxin families. The most highly expressed toxin family was the SVMP family, accounting for 51.10% of the total toxin expression. The other notable toxins included cysteine-rich secretory proteins (CRISPs, 22.36%), c-type lectins (CTLs and snaclecs, 12.13%), and three-finger toxins (3Ftxs, 6.36%). Phylogenetic analyses indicated that SVMPs, CRISPs, and three-finger toxins (3FTxs) are evolutionarily conserved within Colubridae, whereas CTLs likely arose through convergent evolution. All identified SVMPs were classified as P-III type, with one sequence displaying a unique deletion distinct from conventional truncation patterns. The predominantly expressed CTLs are more likely to combine into dimers, exerting coagulation activity. This study provides an insight into the toxin gene expression in the Duvernoy’s gland of R. lateralis, which will benefit future research into the ecological and pharmacological significance of toxins in the genus Rhabdophis. Full article

Phage-encoded Shiga toxin (Stx) released by Shiga toxin-producing E. coli (STEC) can kill multiple eukaryotic bacterial predators, including Acanthamoeba castellanii, Tetrahymena thermophila and Caenorhabditis elegans. However, the impact of Stx type, Stx amount, and the serogroup of the E. coli on the effectiveness of this exotoxin are poorly understood. These factors impact the severity of Stx-mediated disease in humans and therefore, by studying their role in modulating predator–prey interactions, we may gain insight into how these virulence factors evolved to contribute to human pathogenicity. Herein, we investigated the effects of these factors on predator killing by measuring the efficiency with which five different hemolytic uremic syndrome (HUS)-causing STEC strains consume and/or kill A. castellanii and C. elegans. These strains express various combinations of Stx types and amounts and O-antigens. We found that variations in Stx types and amounts significantly affect the ability of a given bacterial strain to kill predator A. castellanii and C. elegans, with higher Stx1 titers (HUSEC 31 vs. 19) and the presence of Stx2 alone (HUSEC 20) correlating with significantly greater predator killing. These attributes also affect STEC pathogenicity in humans, suggesting that ecological selective pressures for anti-predator defense inadvertently drive the evolution of strains with higher virulence potential in humans. Full article

The French Society for Toxinology (SFET) held its 31st annual meeting (RT31) on 1–2 December 2025 at Hôtel Le Saint Paul in Nice, France, on the famous French Riviera. The meeting, which gathered 75 participants from around the world, was organised there for the second consecutive year, while previous editions were all held in Paris. The RT31 main theme, “Toxins: Playing with and fighting them”, explored recent, cutting-edge research in the field of animal venoms and of toxins from algal, animal, bacterial, fungal, plant and microbial origins, in emphasizing the evolution of the toxins, their modes of action and roles, and ways of counteracting intoxinations. These key topics were largely covered through 26 oral and 18 poster communications, organized into three main thematic areas covering three specific aspects of toxinology, along with a traditional fourth, more general session enabling participants to present recent data outside of these themes but nevertheless providing valuable information to the field. This report presents the abstracts of nine of the invited lectures, 14 of the selected lectures, and 16 of the posters, in accordance with the authors’ agreement to publish them. Also, we announce the winners of the “Best Oral Communication” and “Best Poster Communication” awards, which recognize the outstanding contributions of young researchers and their inventive work in toxinology. Full article

Passive transplacental immunity is crucial for neonatal protection from infections. Following Clostridioides difficile (C. difficile) infection, infants do not develop disease, although C. difficile colonization is highly prevalent in infants. This work aimed to characterize humoral immunity specific to C. difficile toxins TcdA and TcdB and to surface proteins FliD and Cwp84, well-known colonizing factors, in pregnant women and their neonates. Anti-C. difficile antibodies were measured in maternal serum, cord blood, and breast milk from 58 healthy pregnant women and their newborns, enrolled in a prospective study, using a quantitative ELISA. Anti-C. difficile antibodies were also measured in pregnant women with C. difficile infection (CDI) in a retrospective peripartum case series. We found a high seroprevalence of IgG specific to the four antigens in healthy pregnant women, regardless of colonization by C. difficile. However, pregnant women exhibited lower concentrations of TcdA-specific IgG antibodies compared to age-matched non-pregnant women. A strong positive correlation between maternal and cord blood IgG specific to TcdA, TcdB, FliD, and Cwp84 was observed, suggesting a transplacental transfer of C. difficile-specific IgG antibodies to neonates. In breast milk, a high seroprevalence of IgA specific to the two toxins was detected, and positive correlations between maternal serum and breast milk antibody levels highlight a preferential transfer of TcdB-specific IgG and Cwp84-specific IgG to breast milk, providing the infant with a protective barrier against C. difficile. Lastly, since pregnant women are at increased risk for C. difficile infection (CDI), we characterized the specific antibody response in a retrospective peripartum case series. Sera from peripartum women with CDI exhibited similar median concentrations of TcdA, TcdB, FliD, and Cwp84 IgM and IgG to those of healthy pregnant women. Moreover, except for one case, antibody concentrations remained stable during the longitudinal evolution of C. difficile response before and after diagnosis of CDI, without any booster effect. Altogether, these data are consistent with antibody-mediated maternal protection of neonates from C. difficile-associated disease. Larger studies exploring immune factors involved in protection from C. difficile-associated disease during pregnancy are needed. Full article

Background: Three-finger toxins (3FTxs) are a major axis of functional diversification in advanced snake venoms, with canonical paralytic activity mediated through muscle-type nicotinic acetylcholine receptors (nAChRs) and a broader set of non-nicotinic targets. This review integrates evidence bearing on coevolution between 3FTxs and target receptors, spanning toxin origin, diversification, receptor evolution, and ecological context. Methods: The synthesis draws on comparative genomic and transcriptomic studies of 3FTx gene-family evolution, codon-model analyses of selection, structural characterisation of toxin–receptor interfaces, and functional assays (including receptor-mimicking peptide binding) that link sequence variation to binding and toxicity. Results: Across lineages, 3FTx diversification is repeatedly structured by strong constraint on the disulphide-rich scaffold with accelerated change concentrated in solvent-exposed loops, alongside birth–death dynamics and exon/segment-level innovation that expand binding specificity. On the receptor side, resistance-associated variation is most intensively characterised for the nAChR α₁ orthosteric site and includes convergent, mechanistically distinct solutions such as electrostatic repulsion and glycosylation-mediated steric interference. Within the predominantly elapid systems currently examined, integrative datasets indicate that prey-selective binding and geographically variable susceptibility can arise from modest substitutions at toxin–receptor interfaces, but they also reveal substantial taxonomic and target-specific biases. Conclusions: Current evidence supports adaptive diversification in both toxins and receptors, while broader evolutionary interpretations are limited by uneven sampling and the frequent lack of matched toxin and receptor variants analysed within a common evolutionary framework. Development of predictive models will require joint pipelines linking genomics, structure-informed evolutionary inference, scalable functional assays, and explicit ecological network context. Full article

The scorpion family Buthidae, renowned for its neurotoxin-rich venoms, dominates toxinology, while non-buthid venoms remain largely unexplored. Here, we present a comprehensive proteomic and biochemical characterization of the Amazonian chactid scorpion Brotheas amazonicus venom (BamazV), with emphasis on molecular complexity, proteolytic processing, and peptide diversity. Using an integrative venomics approach that combines molecular mass-based fractionation, reversed-phase chromatography, high-resolution mass spectrometry, N-terminal sequencing, and functional and immunological analyses, we reveal an unexpectedly complex venom profile enriched in high-molecular-weight components and extensively processed peptides, with more than 40 venom peptides sequenced by MS/MS and Edman degradation. The data provide evidence for non-canonical proteolytic events, including the generation of peptides from precursor regions not classically associated with mature venom components. In contrast to the venom of Tityus serrulatus, BamazV displays a “hydrolase-rich, neurotoxin-poor” profile, featuring a catalytically active Group III phospholipase A₂ (BamazPLA₂), a highly active hyaluronidase, metalloproteases, low-mass peptides, and potassium channel toxins. Our results suggest a hydrolytic prey-subjugation strategy, and limited cross-reactivity with commercial antivenom highlighted its distinct structural landscape. Overall, this study advances the understanding of venom evolution and proteolytic diversification in underexplored scorpion lineages, positioning B. amazonicus as a valuable model for investigating alternative venom strategies and identifying novel biotechnological scaffolds. Full article

Bt Cry toxins remain the cornerstone of transgenic crop protection against Lepidopteran pests, yet field-evolved resistance, particularly in invasive species such as Spodoptera frugiperda and Helicoverpa armigera, can threaten their long-term efficacy. This review presents a comprehensive and unified mechanistic framework that synthesizes current understanding of Bt Cry toxin modes of action and the complex, multilayered regulatory mechanisms of field-evolved resistance. Beyond the classical pore-formation model, emerging evidence highlights signal transduction cascades, immune evasion via suppression of Toll/IMD pathways, and tripartite toxin–host–microbiota interactions that can dynamically modulate protoxin activation and receptor accessibility. Resistance arises from target-site alterations (e.g., ABCC2/ABCC3, Cadherin mutations), altered midgut protease profiles, enhanced immune regeneration, and microbiota-mediated detoxification, orchestrated by transcription factor networks (GATA, FoxA, FTZ-F1), constitutive MAPK hyperactivation (especially MAP4K4-driven cascades), along with preliminary emerging findings on non-coding RNA involvement. Countermeasures now integrate synergistic Cry/Vip pyramiding, CRISPR/Cas9-validated receptor knockouts revealing functional redundancy, Domain III chimerization (e.g., Cry1A.105), phage-assisted continuous evolution (PACE), and the emerging application of AlphaFold3 for structure-guided rational redesign of resistance-breaking variants. Future sustainability hinges on system-level integration of single-cell transcriptomics, midgut-specific CRISPR screens, microbiome engineering, and AI-accelerated protein design to preempt resistance trajectories and secure Bt biotechnology within integrated resistance and pest management frameworks. Full article

Megalomyrmex ant species have a rich natural history that provides an interesting backdrop to understanding how venom has been shaped by evolution. However, like many other species in the tribe Solenopsidini, alkaloid investigations have dominated, limiting our understanding of the diversity of venom components. Here we use transcriptomics to qualify and quantify the proteins and peptides within Megalomyrmex milenae, a species of ant native to the Panamanian rainforest along the Panama Canal. RNA transcripts associated with and over-expressed in the venom gland allow the description of putative toxins and other significant protein components of the venom cocktail. Among other constituents, we find signatures for pore-forming toxins, neurotoxins, carbohydrate-digesting enzymes, proteins which potentially enhance trail pheromone efficacy, and peptides implicated in antimicrobial activity. This work greatly enhances our understanding of Megalomyrmex venoms, showing a multifaceted functional venom profile similar to other ant species. However, proteomic and functional assays are needed to clarify the venom functions hypothesized in this work. Full article

Saxitoxin (STX) is one of the most potent marine neurotoxins, produced by several species of freshwater cyanobacteria and marine dinoflagellates. Although omics-based approaches have advanced our understanding of STX biosynthesis in recent decades, the origin, regulation, and ecological drivers of STX in dinoflagellates remain poorly resolved. Specifically, dinoflagellate STX biosynthetic genes (sxt) are extremely fragmented, inconsistently expressed, and unevenly distributed between toxic and non-toxic taxa. Environmental studies further report inconsistent relationships between abiotic factors and STX production, suggesting regulation across multiple genomic, transcriptional, post-transcriptional, and epigenetic levels. These gaps prevent a comprehensive understanding of STX biosynthesis in dinoflagellates and limit the development of accurate predictive models for harmful algal blooms (HABs) and paralytic shellfish poisoning (PSP). Artificial intelligence (AI), including machine learning and deep learning, offers new opportunities in ecological pattern recognition, molecular annotation, and data-driven prediction. This review explores the current state of knowledge and persistent knowledge gaps in dinoflagellate STX research and proposes an AI-integrated multi-omics framework highlighting recommended models for sxt gene identification (e.g., DeepFRI, ProtTrans, ESM-2), evolutionary reconstruction (e.g., PhyloGAN, GNN, PhyloVAE, NeuralNJ), molecular regulation (e.g., MOFA+, LSTM, GRU, DeepMF), and toxin prediction (e.g., XGBoost, LightGBM, LSTM, ConvLSTM). By integrating AI with diverse biological datasets, this novel framework outlines how AI can advance fundamental understanding of STX biosynthesis and inform future applications in HAB monitoring, seafood safety, and PSP risk management in aquaculture and fisheries. Full article

Tetrodotoxin (TTX) is an extremely potent neurotoxin, a selective blocker of voltage-gated sodium (NaV) channels, produced by bacteria and accumulated across a wide range of taxa. Several TTX-bearing animals have developed molecular adaptations in their NaV channels that provide TTX resistance, making this toxin one of the factors of molecular evolution. However, the molecular basis of TTX resistance in NaV channels of a significant proportion of tetrodotoxic species remains poorly studied. Nemertea is a phylum of marine worms, comprising both TTX-bearing and non-TTX-bearing species. Here, we analyzed the amino acid sequences of the NaV1 channel regions responsible for TTX binding from 22 species of nemerteans. Substitutions previously characterized as conferring TTX resistance in other taxa were detected in sixteen nemerteans; local clustering was observed within several families. These findings suggest that TTX resistance in nemerteans evolved multiple times independently and may serve as either as an adaptation facilitating TTX accumulation for subsequent use for defense and predation, or as a mechanism allowing consumption of tetrodotoxic prey without toxin accumulation. Full article