On-resin assembly of cysteine-reactive linkers for controlled site-selective antibody bioconjugation
Nat Protoc. 2026 Jun 9. doi: 10.1038/s41596-026-01376-4. Online ahead of print.
ABSTRACT
Antibody conjugates represent key advances in targeted biotherapeutics, combining the precision of antibodies with a range of functional payloads, including cytotoxic small molecules, enzymes and peptides, to achieve high selectivity, reduced off-target effects and an improved therapeutic window compared with conventional small-molecule drugs. Here we present a protocol for the solid-phase synthesis of tetra-divinylpyrimidine (tetraDVP) linkers, a modular and scalable strategy for generating cysteine-reactive linkers used in site-selective bioconjugation, enabling the rapid production of diverse antibody conjugates. This protocol describes a multistep synthetic workflow involving solution-phase intermediate synthesis, solid-phase assembly on resin, polyethylene glycol elongation, installation of divinylpyrimidine warheads, and mild cleavage conditions, enabling reproducible production of the final linker scaffold. TetraDVP linkers are designed to simultaneously rebridge all four interchain disulfide bonds of native IgG1 and IgG4 antibodies with a single molecule, enabling the controlled installation of functional payloads such as peptides, drugs or protein tags with controlled payload-to-antibody ratio. This approach provides the only reported strategy for conjugating a single payload to a native antibody without the need for chromatographic purification or genetic/glycan engineering. Compared with previous solution-phase routes, this solid-phase protocol improves yield, scalability and reproducibility while enabling rapid diversification of linker architecture. The complete procedure can be performed in ~2 weeks and provides a versatile platform for accessing tetraDVP linkers bearing a variety of functional handles for antibody conjugation.
PMID:42265460 | DOI:10.1038/s41596-026-01376-4
Testing the drivers of environmental persistence in bacterial pathogens
Microbiology (Reading). 2026 Jun;172(6). doi: 10.1099/mic.0.001713.
ABSTRACT
Bacterial pathogens can increase transmission opportunities by surviving in the external environment, but despite wide variation in this ability, the drivers of such differences remain poorly understood. Here, we comparatively analysed data from 47 studies on 29 bacterial pathogens to investigate how phylogeny, structural traits (cell wall structure), life history (transmission mode, lifestyle, generation time) and abiotic conditions (temperature, humidity and surface material) influence persistence following deposition on inert surfaces. Our results showed that bacterial species differ consistently in persistence, but not in a way predicted by phylogeny. Of the bacterial traits, cell wall structure had a significant effect, with Gram-positive bacteria showing longer survival times. In contrast, transmission mode, lifestyle and generation time had no consistent effect on persistence. Bacteria also survived longer on inorganic surfaces, but with no significant effect of temperature or humidity. These findings indicate that both bacterial structural traits and abiotic conditions may play crucial roles in shaping bacterial persistence in the environment, likely through effects on resistance to hypoosmotic stress. How the benefits of persisting in dry external environments, for instance, by harbouring a Gram-positive cell wall, trade off with survival in hyperosmotic conditions or in the face of immune defences, however, remain to be determined.
PMID:42258372 | DOI:10.1099/mic.0.001713
Antigenic characterization of SARS-CoV-2 variants BA.3.2.1 and BA.3.2.2 in three animal models
bioRxiv [Preprint]. 2026 May 26:2026.05.24.727525. doi: 10.64898/2026.05.24.727525.
ABSTRACT
BA.3.2, a variant of SARS-CoV-2 containing ~40 mutations in its spike protein compared to its nearest ancestor, has spread globally since its first detection in South Africa in November 2024. Here, we report antigenic characterization of BA.3.2 viruses in three naive animal models, and visualize its antigenic phenotype in the context of SARS-CoV-2 evolution using antigenic cartography. We find that: (1) BA.3.2 is substantially antigenically divergent from existing SARS-CoV-2 variants; (2) infection with BA.3.2 in hamster and mouse animal models produces sera with lower homologous titer than infection with other variants. Both of these results may have implications for the selection of vaccine antigens.
PMID:42244675 | PMC:PMC13232355 | DOI:10.64898/2026.05.24.727525
Disrupting phage liquid crystalline droplets restores antibiotic susceptibility in Pseudomonas aeruginosa biofilms
PLoS Biol. 2026 Jun 5;24(6):e3003834. doi: 10.1371/journal.pbio.3003834. Online ahead of print.
ABSTRACT
All bacterial biofilms contain an extracellular matrix rich in filamentous molecules that self-associate, conferring emergent properties to bacteria, including antibiotic tolerance. Pseudomonas aeruginosa is a human pathogen that forms biofilms in diverse infectious settings, where the upregulation of a filamentous bacteriophage Pf4, has been shown to be a key virulence factor that protects bacteria from antibiotics. Here, we modeled biophysical characteristics of biofilm-linked liquid crystalline droplets formed by Pf4, which predicted that sub-stoichiometric phage binders had the ability to disrupt liquid crystals by changing the surface properties of the phage. We tested this prediction by developing nanobodies targeting the outer surface of the Pf4 phage, which disrupted in vitro reconstituted droplets, promoted antibiotic diffusion into bacteria, disrupted P. aeruginosa biofilm formation under a variety of conditions, and abolished antibiotic tolerance of biofilms. The inhibition strategy illustrated in this study could be extended to biofilms of other pathogenic bacteria, where filamentous molecules are pervasive in the extracellular matrix. Furthermore, our findings exemplify how targeting a biophysical mechanism, rather than a defined biochemical target, is a promising avenue for intervention, with the potential of applying this concept to other disease-related contexts.
PMID:42247470 | DOI:10.1371/journal.pbio.3003834
De novo design of RNA pseudoknots with deep learning
bioRxiv [Preprint]. 2026 May 22:2026.05.21.726960. doi: 10.64898/2026.05.21.726960.
ABSTRACT
RNA design has been hindered by the limited accuracy of 3D structure prediction. Here, we show that intricate RNA structures can be generated with current deep learning tools through accurate de novo design of pseudoknot secondary structures. In an Eterna competition involving 57 pseudoknots, generative AI methods matched experienced human designers in solving most blind challenges, evaluated by single-nucleotide-resolution chemical mapping, compensatory mutagenesis, and cryogenic electron microscopy. Unexpectedly, AI-generated molecules with accurate secondary structures formed well-ordered 3D folds stabilized by noncanonical tertiary interactions not modeled during design. Success was guided by a RNet foundation model trained on prior chemical mapping data, suggesting that some difficult RNA design tasks may be tractable without first solving RNA 3D structure prediction.
PMID:42239184 | PMC:PMC13228335 | DOI:10.64898/2026.05.21.726960
Alternative splicing broadens antiviral diversity at the human OAS2 locus
EMBO J. 2026 Jun 3. doi: 10.1038/s44318-026-00825-w. Online ahead of print.
ABSTRACT
Interferons (IFN) are cytokines that regulate the expression of hundreds of genes during viral infections to generate a broadly antiviral environment in the stimulated cell. Antiviral breadth is provided by the concurrent expression of many individual IFN-stimulated genes (ISG), each encoding a protein with often exquisite antiviral specificity. Here, we identify mechanistic plasticity at a single genetic locus as a novel mechanism to diversify the antiviral profile of human cells. Through alternative splicing, the OAS2 gene encodes two antiviral molecules with distinct target specificities. The shorter OAS2 p69 isoform restricts seasonal human coronavirus OC43 (HCoV-OC43), whereas the longer p71 isoform restricts picornavirus Cardiovirus A (EMCV). The restriction profile is determined by the variable length OAS2 C-terminal tails. Notably, these antiviral activities differ in their dependence on RNase L, suggesting that alternative splicing separates canonical restriction and virus sensing functions across two distinct OAS2 polypeptides. Together, these findings show how alternative splicing expands antiviral diversity at the human OAS2 locus.
PMID:42236548 | DOI:10.1038/s44318-026-00825-w
Avian Influenza in Humans: Virology, Transmission, and Clinical Priorities
QJM. 2026 May 29:hcag138. doi: 10.1093/qjmed/hcag138. Online ahead of print.
ABSTRACT
Avian influenza continues to evolve as a zoonotic threat with important implications for clinical practice and global health preparedness. Sustained circulation in wild birds, repeated spillover into poultry, and an increasing number of infections across diverse mammalian hosts have reshaped exposure pathways and broadened the risk landscape for human infection. For clinicians, this evolving ecology translates into atypical presentations and increased diagnostic uncertainty. Recent global activity has been characterised by widespread animal outbreaks and the emergence of new transmission interfaces, including occupational exposures and livestock-associated events. Human infections remain largely zoonotic and geographically heterogeneous, with patterns influenced by surveillance intensity, exposure context, and healthcare access. We synthesise current evidence on the virology, transmission, global epidemiology, clinical manifestations, diagnosis, treatment, and prevention of avian influenza in humans. We highlight evolving mammalian adaptation and changing risk interfaces that complicate risk assessment. Improved clinician awareness, early diagnosis, and integrated One Health surveillance remain central to strengthening preparedness for future influenza threats.
PMID:42213088 | DOI:10.1093/qjmed/hcag138
The epidemiology of wild-crop interfaces: integrating ecology, evolution and management through modelling
Philos Trans R Soc Lond B Biol Sci. 2026 May 28;381(1951):20250110. doi: 10.1098/rstb.2025.0110.
ABSTRACT
Plant diseases occurring across wild and crop plants present modelling and management challenges. Wild plant and crop pathosystems differ in ecological structure, evolutionary dynamics and responsiveness to human intervention. At the interface, pathogens may spill over, spill back, persist or evolve, shaped by host diversity, dispersal processes and landscape connectivity. The potential importance of factors including pathogen dispersal, host life history and spatial configuration are examined through a qualitative comparison of case studies: Puccinia graminis, Phakopsora pachyrhizi, Xylella fastidiosa, Pyricularia oryzae Triticum lineage and Austropuccinia psidii. These examples illustrate how wild hosts may function as reservoirs, recombination partners or spillover targets, and how their role influences management efficacy and evolutionary risk. We explore the consequences of this wild-crop interface through two central questions: (i) how should plant diseases involving wild and cultivated pathosystems be managed, and (ii) what proportion of management effort should be allocated to each system? We show the principles underpinning answers to these questions via a conceptual framework based on a generic compartmental model incorporating asymmetric transmission and system-specific interventions, thereby accounting for key aspects of pathogen spread within and between wild host and crop populations. Finally, we identify critical data needs and modelling directions to better inform disease management on the wild plant-crop interface and argue for a more integrative approach bridging ecological and anthropogenic drivers of epidemics. This article is part of the theme issue 'Wild plant pathosystems'.
PMID:42206329 | DOI:10.1098/rstb.2025.0110
Association of climate change with the spread of antimicrobial resistance genes in Salmonella: a longitudinal ecological and modelling study
Lancet Planet Health. 2027 Mar 3:101445. doi: 10.1016/j.lanplh.2026.101445. Online ahead of print.
ABSTRACT
BACKGROUND: Antimicrobial resistance (AMR) emerges primarily through antibiotic exposure and the resulting selection pressure, but climate change is likely to accelerate the dissemination of AMR, particularly for zoonotic diseases, such as those caused by Salmonella. However, the link between climatic factors and antimicrobial resistance genes (ARGs) carried by Salmonella remains poorly characterised. This longitudinal ecological study aimed to link climate change to ARGs using multiple regression models.
METHODS: We analysed a comprehensive dataset of 488 232 Salmonella genomes and multiple potential predictors from 139 countries or regions over the period 1940-2023. Robustness was verified via Tobit and generalised additive models. Climate-related changes of average ARG abundance in Salmonella were quantified through counterfactual scenarios. Future ARG trends were projected to 2100 using integrated Shared Socioeconomic Pathways (SSPs) with Representative Concentration Pathways scenarios (SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5).
FINDINGS: The global average ARG abundance in Salmonella has increased by 38% (0·50 copies per cell) in the time period considered. Multiple regression models revealed that variability in ARGs follows a non-linear quadratic response to temperature and precipitation. Climate change is associated with a 10% (95% CI 5·4-13·3) global rise in the abundance of Salmonella ARGs, with increases observed in 82 (82%) of 100 countries. By 2100, the emergence of ARGs is projected to be further intensified by warming; however, achieving low-emission (SSP1-2.6) targets alongside strengthened antibiotic stewardship programmes could reduce Salmonella ARGs by 24% (95% CI 21-29) as compared with high-emission scenarios (SSP5-8.5).
INTERPRETATION: This study provides global evidence linking climate change to ARG dynamics in Salmonella. Warming and shifting precipitation patterns are associated with rising ARG abundance and are projected to further exacerbate AMR risks under high-emission scenarios (SSP2-4.5, SSP3-7.0, and SSP5-8.5). These findings highlight the need to integrate climate considerations into AMR surveillance and stewardship, providing a quantitative basis for climate-informed strategies to restrict future resistance escalation.
FUNDING: National Key Research and Development Program of China, the National Natural Science Foundation of China, Zhejiang Provincial Natural Science Foundation of China, and Beijing Municipal Sci-Tech Project on Ecology and Environment.
PMID:42190676 | DOI:10.1016/j.lanplh.2026.101445
Extracellular electron transfer by the cultured coral photosymbiont Symbiodinium microadriaticum
Photosynth Res. 2026 May 25;164(3):31. doi: 10.1007/s11120-026-01218-0.
ABSTRACT
Photosynthetic microorganisms may show extracellular electron transfer (EET), in which some of the electrons generated by photosynthesis or respiration are lost from the cell. Most studies have focussed on cyanobacteria, with very few on eukaryotic algae. Here we demonstrate EET from the eukaryotic dinoflagellate alga Symbiodinium microadriaticum, a species that can form symbiosis with corals and other Cnidaria. We show that the EET involves diffusible electroactive species, which may represent a previously unsuspected route for communication between symbionts and hosts. We show that EET can be used to study photosynthetic and respiratory functions in the dinoflagellate. We also show that it can provide information on the effects of environmental stresses including changes in temperature (linked to coral bleaching), pH and light intensity. The electrochemical platform outlined in this study offers a novel tool for studying dinoflagellate physiology, the coral-dinoflagellate symbiosis, and the molecular mechanisms of bleaching.
PMID:42184070 | DOI:10.1007/s11120-026-01218-0
Reducing Supply Chain Dependencies for Viral Genomic Surveillance: Get by with a Little HELP from Commercial Enzymes already in your Lab Freezer
Wellcome Open Res. 2025 Oct 1;10:529. doi: 10.12688/wellcomeopenres.24735.1. eCollection 2025.
ABSTRACT
BACKGROUND: The COVID-19 pandemic exposed critical vulnerabilities in global laboratory supply chains, disrupting the availability of key reagents and jeopardising the continuity of genomic surveillance essential for epidemic response. Sustaining sequencing capacity during supply shortages requires practical, locally accessible alternatives to commercial kits.
METHODS: We developed ARTIC HELP (Homebrew Enzymes for Library Preparation), an open-source adaptation of the ARTIC nanopore sequencing protocol for viral genomic surveillance. We described cost-effective, generic replacements for all enzyme mixes used in tiling multiplex RT-PCR and the nanopore native barcoding workflow, including end-prep (EP), barcode ligation (BL), and adapter ligation (AL). Through systematic evaluation, we tested wild-type M-MLV reverse transcriptase and two types of proofreading DNA polymerases, (i) B-family Pfu-based polymerases fused to an Sso7d DNA-binding domain, and (ii) blends of A-family (Taq-based) and B-family (Pfu-based) polymerases, against standard reagents. We validated the workflow on clinical SARS-CoV-2 and Norovirus GII samples.
RESULTS: The HELP workflow delivered genome coverage comparable to the ARTIC LoCost protocol. For SARS-CoV-2 samples (Ct ≤28), wild-type M-MLV RT combined with selected Pfu or AB blend polymerases, alongside optimized HELP EP, BL, and AL mixes, achieved 84.0-99.6% genome coverage. For Norovirus GII samples (Ct ≤32), the HELP workflow enabled >85% coverage across six of eight genotypes tested. While some polymerases showed reduced performance at higher Ct values, they performed reliably at Ct <24, supporting their use as emergency alternatives in rapid outbreak-response sequencing when viral load is high and RNA quality sufficient.
CONCLUSIONS: ARTIC HELP provides a robust and flexible solution to maintain viral sequencing capacity when standard reagents are inaccessible or unaffordable. Our cost analysis highlights stark global disparities in reagent pricing driven by import fees and supply barriers, rather than protocol complexity, underscoring the need for equitable pricing models and local sourcing strategies. By giving laboratories more options for essential reagents, ARTIC HELP strengthens preparedness and resilience for future public health emergencies.
PMID:42181968 | PMC:PMC13197761 | DOI:10.12688/wellcomeopenres.24735.1
Biochemical characterization of purified apyrases in Arabidopsis thaliana
Plant Physiol Biochem. 2026 May 16;235:111371. doi: 10.1016/j.plaphy.2026.111371. Online ahead of print.
ABSTRACT
Apyrases (nucleoside triphosphate-diphosphohydrolases) are enzymes that regulate the concentration of NTP and NDP nucleotides in cells by removing their terminal phosphate. Two of the 7 apyrases in Arabidopsis, APY1 and APY2, are 87% identical in primary structure and play important roles in regulating auxin transport and plant growth. To clarify how these apyrases function, this report confirms their localization in purified nuclei and characterizes their enzymatic properties. Immunolocalization and immunoblot assays using a polyclonal antibody (2556) raised to a 24-mer peptide unique to APY1 showed that this calmodulin-binding APY was highly expressed in nuclei purified from etiolated Arabidopsis seedlings, just as a previously characterized calmodulin-binding apyrase, psNTP9, is highly expressed in purified nuclei of etiolated pea seedlings. Crude nuclear extracts assayed by mass spectroscopy identified the presence of APY1. Because nuclei purified from seedlings expressing APY1-GFP and APY2-GFP both showed the GFP signal, both APY1 and APY2 were likely present in the final preparation of APY, which eluted as a 48 kDa monomer from a molecular sieve column. As estimated by silver-staining after its separation on SDS-PAGE, the purified APY was >85% pure. It had a specific activity toward ATP and ADP substrates similar to that of other apyrases purified from plant and animal sources, but did not hydrolyze AMP substrates. These results favor those of prior reports that APY1/2 are nucleoside triphosphate-diphosphohydrolases, but differ from those of an earlier report that found HA-tagged APY1 extracted from light-grown Arabidopsis tissue did not hydrolyze ATP.
PMID:42176408 | DOI:10.1016/j.plaphy.2026.111371
Machine learning framework for cost effective deep mutational scanning through targeted substitution profiling
BMC Bioinformatics. 2026 May 19. doi: 10.1186/s12859-026-06473-5. Online ahead of print.
ABSTRACT
BACKGROUND: Deep mutational scanning (DMS) provides comprehensive maps of protein variant effects but remains experimentally intensive. Machine learning (ML) approaches have the potential to reduce experimental burden of DMS by predicting the functional impact of substitutions from limited data.
RESULTS: We introduced a ML classifier trained on normalised DMS scores from SARS-CoV-2 main protease (Mpro) to categorise amino acid substitutions as functional (wild-type-like) or non-functional. Using brute-force feature selection, we identified minimal subsets of six substitution scores per residue that enable accurate classification of the remaining substitutions, achieving minimum (worst accuracy) scores exceeding 90%. Models including support vector machines, random forests, and logistic regression were evaluated without retraining (zero-shot prediction) against additional SARS-CoV-2 Mpro datasets and against unrelated datasets. The zero-shot performance of the models was strongest for other enzymes and more modest when applied to DMS systems that assess protein folding and/or protein-protein interactions.
CONCLUSION: The results show that targeted DMS combined with ML can reduce sequencing and reagent costs while preserving classification accuracy, offering a practical route to accelerate variant effect prediction.
PMID:42157089 | DOI:10.1186/s12859-026-06473-5
A phase I, needle free, dose escalation clinical trial of pEVAC-PS, a candidate pan-Sarbecovirus Vaccine
J Infect. 2026 May 18:106759. doi: 10.1016/j.jinf.2026.106759. Online ahead of print.
ABSTRACT
BACKGROUND: Coronaviruses such as SARS, SARS-CoV-2 and related Sarbeco-Coronaviruses continue to pose global health threats, underscoring the need for vaccines capable of inducing broad cross-sarbecovirus protection. The pEVAC-PS vaccine was developed using Digitally Immune Optimised Synthetic Vaccine (DIOSynVax) technology and pre-clinically selected for the ability to induce broadly protective immune responses across the Sarbecoviruses including SARS, SARS-CoV-2, and related viruses representing potential zoonotic spillovers. For this first-in-human study, the antigen was delivered as a DNA vaccine to enable thermostability and needle-free intradermal administration to support future deployment in resource-limited settings.
METHODS: This open label phase I dose escalation study investigated the safety, tolerability and immunogenicity of the pEVAC-PS vaccine candidate against SARS, SARS-CoV-2 and related Sarbeco Coronaviruses via needle-free intra-dermal delivery using the PharmaJet Tropis Device. Healthy volunteers aged 18 to 50 who had received two or three prior doses of COVID-19 vaccine, and without recent confirmed COVID-19 infection, were enrolled sequentially to receive a dose escalation regime of 0.2mg, 0.4mg, 0.8mg, and 1.2mg of pEVAC-PS, administered at day zero and day 28. The primary outcomes were safety and reactogenicity, documented by solicited and unsolicited adverse events, serious adverse events and adverse events of special interest. Secondary outcomes were immunogenicity measured primarily by humoral responses to SARS-CoV-1 and SARS-CoV-2 antigens at day 56 (28 days after the second dose of vaccine). International Clinical Trials Registry Platform registered, ISRCTN87813400.
FINDINGS: Between December 2021 and September 2023, a total of 39 volunteers were vaccinated. The vaccine was well tolerated at all four doses with no significant safety concerns elicited. Interpretation of immunogenicity outcomes was influenced by high baseline antibody levels and heterogeneous exposure histories due to ongoing waves of Omicron variant infections during recruitment, which differed across dose-escalation cohorts and introduced unavoidable immune bias.
INTERPRETATION: Needle-free intradermal delivery of this novel computationally designed PanSarbeco vaccine was safe and well tolerated. Although immunogenicity was modest in the context of substantial pre-existing immunity, participants developed measurable responses to conserved, vaccine-encoded sarbecovirus epitopes, supporting the feasibility of this antigen design strategy.
PMID:42155675 | DOI:10.1016/j.jinf.2026.106759
Cell surface localisation of GPI-anchored receptors in <em>Trypanosoma brucei</em>
Elife. 2026 May 19;14:RP107191. doi: 10.7554/eLife.107191.
ABSTRACT
Trypanosoma brucei, the causal agent of Human and Animal African trypanosomiasis proliferates in the extracellular milieu of mammals. It acquires host macromolecular nutrients by receptor-mediated endocytosis. The best characterised cell surface receptor is for transferrin (TfR), and it has been reported to be preferentially localised in the flagellar pocket domain of the plasma membrane, the sole site of endocytosis. In this location, the TfR may be inaccessible to adaptive immune system effectors. The T. brucei genome encodes ~15 TfR variants, and here we compared two, the first attached to the plasma membrane by a single glycosylphosphatidylinositol (GPI)-anchor and the other by two. Transferrin uptake kinetics were similar and rapid for both. Unexpectedly, initial binding of transferrin occurred over the whole cell surface suggesting the TfR was not localised solely in the flagellar pocket. This localisation was confirmed by immunofluorescence assays and was independent of the number of GPI-anchors. Two other GPI-anchored receptors were investigated to determine whether localisation to the whole cell surface was a general property of GPI-anchored receptors. Haptoglobin-haemoglobin uptake assays and immunofluorescence localisation of complement factor H receptor showed both were also whole cell surface localised. The mechanisms by which trypanosome receptors are protected from antibody-mediated attack are more complex than hiding in a pocket.
PMID:42153621 | DOI:10.7554/eLife.107191
Not just another kinase: the many roles of PI3K-δ in adaptive immunity
J Immunol. 2026 May 14;215(5):vkag071. doi: 10.1093/jimmun/vkag071.
NO ABSTRACT
PMID:42153523 | DOI:10.1093/jimmun/vkag071
Host-virus association databases as tools for understanding viral spillover at varying scales
PLoS Negl Trop Dis. 2026 May 18;20(5):e0013343. doi: 10.1371/journal.pntd.0013343. Online ahead of print.
ABSTRACT
Large host-virus association databases are increasingly used to explore broad questions in disease ecology, particularly around host range, pathogen diversity, and the potential for spillover. While these databases have been instrumental in large-scale synthesis of host- pathogen biogeography and zoonotic risk, their potential role in addressing fine-scale questions about pathogen prevalence, maintenance, and transmission dynamics remains underexplored. In this study, we build on previous efforts to assess how different types of data, including both entries in databases and the original studies they draw from, can support targeted research on zoonotic spillover. We selected two zoonotic diseases, Ebola virus disease and Lassa fever, which are characterised by recurrent spillover events and outbreaks in sub-Saharan Africa. We searched the VIRION database for entries corresponding to the respective viral taxa, the genus Orthoebolavirus and the species Mammarenavirus lassaense, and used these entries as case studies. We evaluated the extent to which databases capture crucial contextual metadata, such as spatial and temporal resolution, negative results, and measures of viral load. Guided by a conceptual framework of factors that lead to spillover, we demonstrate that while host- virus databases are valuable for addressing high-level patterns, fine-scale investigations of spillover require specific studies with detailed epidemiological data. Our study adds to a growing body of literature offering practical recommendations for database users and managers and highlights how these tools can be used as starting points in spillover research.
PMID:42149938 | DOI:10.1371/journal.pntd.0013343
Characterization of <em>Ornithobacterium hominis</em> colonization dynamics and interaction with the nasopharyngeal microbiome in a South African birth cohort
Microb Genom. 2026 May;12(5). doi: 10.1099/mgen.0.001635.
ABSTRACT
Ornithobacterium hominis is a recently described Gram-negative bacterium that colonizes the human nasopharynx and may be associated with poor upper respiratory tract health. Here, we describe the isolation of O. hominis from samples collected from a South African birth cohort, creating the first archive of cultured strains of the species from Africa. Sequenced genomes from this archive reveal that South African O. hominis is more similar to Australian strains than those from Southeast Asia and that it may share genes with other members of the microbiome that are relevant for virulence, colonization and antibiotic resistance. Leveraging existing microbiome data from the cohort, O. hominis was found to be closely associated with bacterial co-colonizers that are rare in non-carrier individuals, including Suttonella, Rappaport, Helcococcus, Lwoffella, Moraxella and Gracilibacteria. Their collective acquisition has a significant impact on the diversity of nasopharyngeal communities that contain O. hominis. Individuals who have not yet acquired O. hominis have a higher abundance of Lwoffella lincolnii than individuals who never acquire O. hominis, suggesting that this could be a precursor state for successful colonization.
PMID:42149113 | DOI:10.1099/mgen.0.001635
Magneto-optical microscopy platform for quantitative imaging of hemozoin in blood for malaria diagnosis
Biomed Opt Express. 2026 Apr 21;17(5):2523-2532. doi: 10.1364/BOE.586641. eCollection 2026 May 1.
ABSTRACT
Malaria remains a major global health challenge, particularly in low-resource settings where diagnostic infrastructure is limited. The gold standard diagnostic is manual light microscopy which is slow, labor-intensive, and dependent on expert interpretation limiting the management of malaria. Here, we present a magneto-optical (MO) imaging approach that exploits the magnetic anisotropy and optical dichroism of hemozoin crystals to achieve label-free, quantitative detection of malaria infection within a conventional polarizing microscope. In our implementation, an external magnetic field induces torque on the paramagnetic hemozoin crystals, aligning their long axes along the field vector. This alignment modulates the optical anisotropy of the specimen, producing a measurable field-dependent change in transmitted polarization contrast. Unlike previously reported standalone magneto-optical devices, which rely on bulk optical scattering or transmission modulation, our approach integrates MO directly into a conventional polarizing microscope setup, allowing simultaneous imaging and quantitative MO signal analysis at the microscopic scale. By integrating ratiometric intensity analysis and threshold-based segmentation metrics, we advance malaria imaging beyond purely observational assessment, enabling a quantitative correlation between MO signal strength and hemozoin concentration, and thus, with parasite developmental stage. These metrics are also well-suited for automated malaria diagnostics, as they provide stable, objective parameters that can be reliably computed without expert intervention. Moreover, because microscopy expertise is already well established in many malaria-endemic regions, embedding this approach within the familiar framework of microscopy offers a practical and rapid pathway for integrating the technique into routine malaria diagnosis.
PMID:42145676 | PMC:PMC13178579 | DOI:10.1364/BOE.586641
CRISPR-based environmental detection of Burkholderia pseudomallei identifies sanitation gaps and melioidosis risk in northeast Thailand
Nat Commun. 2026 May 15. doi: 10.1038/s41467-026-73286-8. Online ahead of print.
ABSTRACT
Environmental exposure to Burkholderia pseudomallei, the causative agent of melioidosis, remains poorly characterised due to the low sensitivity of conventional detection methods. Here, we develop CRISPR-BEEPs, a sensitive and resource-efficient CRISPR-based assay, and evaluate its performance against conventional culture-based plate inspection using double-qPCR as the reference standard. CRISPR-BEEPs demonstrated higher sensitivity (93.5% vs 19.4%) and high specificity (100% vs 98.0%). We apply the assay to water samples from natural and piped sources across 15,118 km² in northeast Thailand, collected from or near the households of 439 participants with melioidosis. We compared these with households of 190 participants with other bacterial infections and 506 healthy control participants living in the same endemic region who had never developed melioidosis. CRISPR-BEEPs detects B. pseudomallei in 73.3% of groundwater, 32.9% of surface water, and 26.2% of piped water samples, with results comparable to double-qPCR. The improved sensitivity reveals a significant association between environmental detection within 10 km of households and melioidosis risk (OR 2.74; 95% CI:1.38-5.48), an association undetectable using conventional methods. These findings expose critical sanitation gaps and highlight the value of high-resolution environmental surveillance for disease prevention.
PMID:42140954 | DOI:10.1038/s41467-026-73286-8