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Journal articlePretorius D, Nikov G, Washio K, et al., 2026,
Designing novel solenoid proteins with in silico evolution
, Communications Chemistry, Vol: 9, ISSN: 2399-3669Solenoid proteins are elongated tandem repeat proteins with diverse biological functions, making them attractive targets for protein design. Advances in machine learning have transformed our understanding of sequence-structure relationships, enabling new approaches for de novo protein design. Here, we present an in silico evolution platform that couples a solenoid discriminator network with AlphaFold2 as an oracle within a genetic algorithm. Starting from random sequences, we design α-, β-, and αβ-solenoid backbones, generating structures that span natural and novel solenoid space. We experimentally characterise 41 solenoid designs, with α-solenoids consistently folding as intended, including one structurally validated design that closely matches the design model. All β-solenoids initially failed, reflecting the difficulty of designing β-strand majority proteins. By introducing terminal capping elements and refining designs based on earlier experimental screens, we generate two β-solenoids that have biophysical properties consistent with their designs. Our approach achieves fold-specific hallucination-based design without depending on explicit structural templates.
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Journal articleKuang X, Gorzynski J, Touchon M, et al., 2026,
Bacteriophages mobilise bacterial defence systems via lateral transduction
, Science Advances, Vol: 12, ISSN: 2375-2548To counter challenges from bacteriophages (phages), bacteria use defense mechanisms that can reside on mobile genetic elements or within chromosomes. These immune systems are easily gained and lost, allowing adaptation to threats. However, the mechanism of mobilization of chromosomally encoded defense genes remains poorly understood. Here, we show that phage- and phage-inducible chromosomal island (PICI)–mediated lateral transduction (LT), a highly efficient horizontal gene transfer mechanism, facilitates the transfer of these defense genes between bacteria. Using several bacterial models, we demonstrate that defense systems are often positioned near phage or PICI attachment sites, allowing them to exploit LT for their mobility. In addition, LT diversifies defense genes carried by prophages and PICIs, driving immune system evolution and turnover. These processes provide phage resistance to new bacterial hosts and profoundly affect population genomics. Our findings reveal LT as a crucial mechanism shaping bacterial evolution and influencing the trajectory of pathogenic clones in nature.
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Journal articleGuo X, Zhang X, Qiu X, et al., 2026,
A Series–Parallel Multiport Flexible Interconnection Topology for AC/DC Distribution Networks
, IEEE Transactions on Power Electronics, Vol: 41, Pages: 4026-4044, ISSN: 0885-8993The use of flexible interconnection technology enhances the power stability in medium-voltage (MV) distribution grids with a high proportion of renewable energy and new loads. It can effectively regulate the power flow of the interconnected distribution grids with a fast response time. This article presents a novel series–parallel power flow control topology flexibly interconnecting a single dc port with multiple ac ports. The dc port provides an additional control degree of freedom, allowing independent control of the active power and reactive power at each ac port. The proposed topology features high modularity and enables easy expansion of the ac ports connected adding only a small number of devices. The operation principle, control strategy, and parameter design of the proposed topology are systematically presented. The feasibility of the proposed topology has been validated based on the PSCAD/EMTDC offline simulation model and the real-time digital simulator experiment model.
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Journal articleRaji YO, Othman MHD, Puteh MH, et al., 2026,
Photocatalytic treatment of final discharge palm oil mill effluent (POME) using dual-layer hollow fiber ceramic membranes with TiO2-embedded mullite: Performance evaluation and mechanistic insights
, Materials Science and Engineering B, Vol: 323, ISSN: 0921-5107The palm oil industry is a key player in global agriculture, but palm oil mill effluent (POME) presents significant environmental concerns due to its high organic load. This study investigates the use of TiO<inf>2</inf>-modified dual-layer (DL) mullite ceramic hollow fiber membranes to improve POME treatment. Single-layer (SL) and DL membranes were prepared via phase inversion and sintering, and characterized using SEM, EDX, ATR-FTIR, XRD, UV–Vis spectroscopy, and flexural strength tests. The effect of TiO<inf>2</inf> loading (1–4 wt%) on DL membrane performance was assessed under UV–Vis irradiation. Results showed DL membranes outperformed SL membranes in photocatalytic activity, fouling resistance, and self-cleaning properties. The DL4 membrane achieved 44.92 % COD removal, 52.40 % colour removal, 54.50 % rejection, and a flux of 18.90 L/m<sup>2</sup>·h·bar. These enhancements are attributed to the synergistic effects of TiO<inf>2</inf> and the dual-layer design, offering an efficient and sustainable strategy for treating POME in compliance with environmental standards.
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Journal articleMorrison AG, Jackson R, Freemont PS, et al., 2026,
An enhanced domestication method for uncultured bacteria.
, ISME Commun, Vol: 6When environmental bacteria transition to laboratory conditions, a process termed domestication, the shift from the native habitat to a culture medium often reduces cell cultivability. Consequently, most bacteria remain uncultured using standard techniques, leaving the majority of their diversity unexplored. Here we introduce an enhanced domestication (EDEN) method for bacterial cultivation, which acclimatises environmental bacteria to culture media through a controlled and gradual exposure. To facilitate EDEN, we develop a 3D-printable microwell plate incorporating growth chambers integrated with a continuous-flow media reservoir. Using amplicon sequencing, we show that EDEN-acclimatised bacterial polycultures grow as distinct populations with significantly greater diversity and likely-uncultured taxa compared with standard cultivation methods. Similarly, EDEN-acclimatised bacterial monocultures show three-fold greater diversity and tenfold more likely-uncultured taxa. EDEN also doubled the cultivability of agarose-encapsulated microcolonies. Finally, we demonstrate the utility of EDEN by isolating a previously uncultured bacterium exhibiting broad-spectrum antimicrobial activity against drug-resistant pathogens.
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Journal articleBiswas P, Sanchez-Garrido J, Kozik Z, et al., 2025,
The accessory type III secretion system effectors collectively shape intestinal inflammatory infection outcomes
, Gut Microbes, Vol: 17, ISSN: 1949-0976Injection of effectors via a type III secretion system (T3SS) is an infection strategy shared by various Gram-negative bacterial pathogens, many infecting mucosal surfaces. While individual T3SS effectors are well characterized, their network-level organization and the distinction between core and accessory effectors remain incompletely understood. Here, by systematically dissecting the T3SS effector network of the enteric mouse pathogen Citrobacter rodentium (CR) we identified a subset of 12 accessory effectors that, while dispensable for colonization, significantly alter infection outcomes. A strain lacking the accessory effectors (CRM12) remained virulent in susceptible mouse hosts yet resulted in reduced epithelial barrier damage, inflammation, and immune cell infiltration in resistant mice. Deep proteomic analysis specifically targeting CR-attached colonic epithelial cells revealed that, despite lacking 39% of its effector repertoire, infection with CRM12 results in similar changes to global protein expression as seen in mice infected with the wild-type strain, though key regulators of barrier integrity were differentially expressed. Using a host with impaired barrier repair (Il22− /− mice), we confirmed that accessory effectors collectively shape infection outcomes without significantly impacting virulence. This study refines the concept of core and accessory effectors, providing a basis for further studies into effector-driven host adaptation.
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Journal articleHerzog MK-M, Peters A, Shayya N, et al., 2025,
Comparing <i>Campylobacter jejuni</i> to three other enteric pathogens in OligoMM<SUP>12</SUP> mice reveals pathogen-specific host and microbiota responses
, GUT MICROBES, Vol: 17, ISSN: 1949-0976- Cite
- Citations: 1
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Journal articlePenadés JR, 2025,
Phage satellites break into the jumbo era.
, Proc Natl Acad Sci U S A, Vol: 122 -
Journal articleConsoli G, Tufail F, Leong HF, et al., 2025,
Locating the missing chlorophylls f in far-red photosystem I
, Science, Vol: 390, ISSN: 0036-8075The discovery of chlorophyll f-containing photosystems, with their long-wavelength photochemistry, represented a distinct, low-energy paradigm for oxygenic photosynthesis. Structural studies on chlorophyll f-containing photosystem I could identify some chlorophylls f sites, but none among the photochemically active pigments and concluded that chlorophyll f plays no photochemical role. Here, we report two cryo-EM structures of far-red PSI from Chroococcidiopsis thermalis PCC 7203, allowing the assignment of eight chlorophylls f molecules, including the redox active A-1B. Simulations of absorption difference spectra induced by charge separation indicate that the experimental spectra can be reproduced only by considering the presence of a chlorophyll f at the A-1B site. The chlorophyll f locations, wavelength assignments, and conserved far-red-specific residues provide functional insights for efficient use of long wavelength photons.
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Journal articleTomkins J, Edwardes L, Faull S, et al., 2025,
Geminin inhibits DNA replication licensing by sterically blocking CDT1-MCM2 interactions
, Nature Communications, Vol: 16, ISSN: 2041-1723DNA replication is tightly regulated to occur once per cell cycle, with the MCM2-7 helicase loaded onto replication origins only during G1-phase. In higher eukaryotes, geminin negatively regulates this process during S-, G2- and M-phases by binding the essential licensing factor CDT1. Although geminin’s function is crucial for genomic stability, its inhibitory mechanism remains elusive. Here, we utilise a fully reconstituted human DNA replication licensing assay to dissect geminin’s role. AlphaFold modelling provides structural insights into an N-terminal CDT1-binding helix of geminin, which proves essential for inhibition. Structural docking of the CDT1-geminin complex into the ORC-CDC6-CDT1-MCM2-7 (OCCM) assembly shows that geminin’s long coiled-coil domain sterically clashes with the MCM2 C-terminus, rather than directly blocking CDT1 binding to ORC-CDC6-MCM2-7. Shortening the coiled-coil preserves geminin dimerisation and CDT1 binding but abolishes inhibition, confirming its mechanistic role. Surprisingly, geminin is not able to fully inhibit DNA licensing. However, CDK1/2-cyclin A can partially inhibit DNA licensing and, in conjunction with geminin, result in a complete block. These findings uncover geminin’s steric inhibitory mechanism and suggest that a dual CDK-geminin axis controls human DNA replication.
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Journal articleKuhlen L, Argunhan B, Liang P, et al., 2025,
RAD51AP1 is a versatile RAD51 modulator
, Proceedings of the National Academy of Sciences, Vol: 122, ISSN: 0027-8424RAD51AP1 is an emergent key factor in homologous recombination (HR), the major pathway for accurate repair of DNA double-strand breaks, and in alternative lengthening of telomeres (ALT). Depletion of RAD51AP1 diminishes HR and overexpression is common in cancer, where it is associated with malignancy. Here, we show that RAD51AP1 has a hitherto unknown role in modulating the RAD51 recombinase, the central player in HR. Through a combination of biochemistry and structural biology, we reveal that RAD51AP1 possesses at least three RAD51-binding sites that facilitate its binding across two adjacent RAD51 molecules. We uncover a previously unidentified RAD51-binding mode that stabilizes the RAD51 N-terminal domain and protomer interface in the filaments. We uncover a previously undescribed role for RAD51AP1 in stabilizing RAD51-ssDNA filaments and promoting strand exchange. Our structural data provide the molecular basis for how RAD51AP1 binding induces conformational changes that promote RAD51 DNA association and oligomerization, therefore promoting filament nucleation, stabilization, and strand exchange. Further, we resolved structures of RAD51-ssDNA filaments in the presence of Mg2+-ATP and upon hydrolysis to Mg2+-ADP, revealing that RAD51 filaments expand upon ATP hydrolysis and explaining how ADP reduces RAD51–DNA binding. Our findings reveal RAD51AP1 as a versatile RAD51 modulator and RAD51 filament remodeler and shed previously unidentified insights into the modulation of HR, which is critical for the maintenance of genome stability.
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Journal articleBigi A, Conti AC, Napolitano L, et al., 2025,
Cellular prion protein and calcium ions trigger the neurotoxicity of α-synuclein aggregates
, CELL AND BIOSCIENCE, Vol: 15 -
Journal articleChilloux J, Brial F, Everard A, et al., 2025,
Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control
, Nature Metabolism, Vol: 7, Pages: 2531-2547, ISSN: 2522-5812The global type 2 diabetes epidemic is a major health crisis. Although the microbiome has roles in the onset of insulin resistance (IR), low-grade inflammation and diabetes, the microbial compounds controlling these processes remain to be discovered. Here, we show that the microbial metabolite trimethylamine (TMA) decouples inflammation and IR from diet-induced obesity by inhibiting interleukin-1 receptor-associated kinase 4 (IRAK4), a central kinase in the Toll-like receptor pathway sensing danger signals. TMA blunts TLR4 signalling in primary human hepatocytes and peripheral blood monocytic cells and rescues mouse survival after lipopolysaccharide-induced septic shock. Genetic deletion and chemical inhibition of IRAK4 result in metabolic and immune improvements in high-fat diets. Remarkably, our results suggest that TMA—unlike its liver co-metabolite trimethylamine N-oxide, which is associated with cardiovascular disease—improves immune tone and glycemic control in diet-induced obesity. Altogether, this study supports the emerging role of the kinome in the microbial–mammalian chemical crosstalk.
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Journal articleLiew CM, Puteh MH, Othman MHD, et al., 2025,
Innovative photothermal membrane distillation: Mitigating temperature polarisation with rice husk biochar
, Journal of Environmental Chemical Engineering, Vol: 13This study presents an innovative dual-layer hollow fibre (DLHF) polymeric membrane for photothermal membrane distillation (PMD), incorporating extracted carbon from rice husk char (RHC) as a sustainable photothermal additive to address two critical challenges in MD desalination: temperature polarisation (TP) and limited flux efficiency. The approach integrates optimisation of pyrolysis temperature, carbon extraction, and performance evaluation of the fabricated membranes. Results revealed that a high pyrolysis temperature (700°C) yielded RHC with enhanced physical properties for photothermal conversion and membrane integration, while a lower temperature (500°C) produced RHC with high carbon content and superior optical traits. RHC synthesised at 600°C provided the best balance of carbon content, particle structure, and light absorption, and was selected for carbon extraction. The extracted carbon (RHC 600-EC) exhibited notable improvements, including a 26.1 % reduction in particle size, a 66.3 % increase in Brunauer–Emmett–Teller surface area, and a 94.4 % rise in total pore volume. It also demonstrated high carbon content (92.3 % by energy-dispersive X-ray analysis, 81.1 % by carbon, hydrogen, nitrogen, and sulfur analysis) and excellent optical properties, with minimal reflectance (< 5 % in the ultraviolet and < 3 % in the visible-near infrared range). The photothermal membrane, fabricated with 5 wt% RHC 600-EC, achieved a 117 % rise in surface temperature and a solar-driven flux of 3.42 kg/m<sup>2</sup>·h under 0.5 kW/m<sup>2</sup> irradiation, representing a 25-fold improvement over the pristine membrane. It further demonstrated a 39.3 % increase in energy efficiency, 59.4 % solar utilisation efficiency, and over 99.5 % salt rejection, highlighting its promising potential for efficient desalination.
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Journal articleBlundell SV, Liu M, Tocci R, et al., 2025,
Mammalian and bacterial adaptors function as co-disinhibitory pairs to activate the E3 ubiquitin ligase WWP2
, Journal of Biological Chemistry, Vol: 301, ISSN: 0021-9258The NEDD4-like E3 ubiquitin ligase, WWP2, is involved in a range of host processes from cell differentiation to T cell immunity. Ligase activity is tightly regulated with WWP2 being held in an autoinhibited state. Binding of a PY motif-containing adaptor, an Ndfip, via the WW domains of NEDD4-like E3 ubiquitin ligases leads to their disinhibition. Here, we show that the canonical Ndfip, NDFIP2, requires multiple PY motifs for interaction with and activation of WWP2. In contrast, the single PY-motif containing Ndfips TMEM127 and SUSD6 function as a co-disinhibitory pair. TMEM127 and the Salmonella protein SteD also function as a co-disinhibitory pair. However, SteD requires a different region of WWP2, the C2 domain, for interaction with WWP2 and this interaction results in disinhibition of WWP2. These findings demonstrate a range of ways that Ndfips can disinhibit WWP2. To our knowledge, these are the first examples of two Ndfips functioning as co-disinhibitory pairs, and of a bacterial effector that disinhibits an E3 ubiquitin ligase.
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Journal articleChen W, Xu J, Tao T, et al., 2025,
Nucleation of high-resolution protein crystals on tailored hydrogel membranes: Secondary conformation transition
, CHEMICAL ENGINEERING JOURNAL, Vol: 525, ISSN: 1385-8947 -
Journal articleOlivieri C, Biancaniello C, Manu VS, et al., 2025,
Protein Kinase A Phosphorylates a Conformationally High-energy State of Raf Kinase Inhibitory Protein q
, JOURNAL OF MOLECULAR BIOLOGY, Vol: 437, ISSN: 0022-2836- Cite
- Citations: 1
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Journal articleBurgaletto C, Cantone AF, Palmas MF, et al., 2025,
Retinal alterations resemble brain pathology in a rat model of Parkinson's disease induced by intranigral infusion of α-synuclein oligomers
, CELL DEATH DISCOVERY, Vol: 11 -
Journal articleEmendato A, Divisato G, Giannino E, et al., 2025,
Structural and cellular properties of human prion protein oligomers
, COMMUNICATIONS BIOLOGY, Vol: 8 -
Journal articleSabnis A, Figueroa W, Santos-López A, et al., 2025,
Non-conjugative plasmids limit their mobility to persist in nature
, Cell reports, Vol: 44, ISSN: 2211-1247Plasmids are mobile genetic elements that disseminate beneficial genes, such as those conferring antibiotic resistance, but the evolutionary forces shaping their distribution remain unclear. This study challenges the idea that non-conjugative plasmids evolved for high-frequency spread. Using Staphylococcus aureus as a model, we found these plasmids lack key DNA sequences (“pac” or “cos” sites) essential for efficient phage-mediated transduction, despite such sequences not being costly. While S. aureus plasmids can evolve to enhance phage-mediated mobility by incorporating phage DNA, this strategy proves detrimental. In mixed populations, low plasmid transfer enables plasmids to coexist and protect host bacteria and neighbours from threats. However, increased movement reduces plasmid diversity, eroding protective benefits and leaving populations vulnerable. Our findings indicate plasmids evolve to restrict movement, maintaining diversity and ensuring survival against threats like antibiotics and phages. This balance explains why plasmid mobility remains low in nature, despite their potential for rapid gene transfer.
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Journal articleFadini A, Apostolopoulou V, Lane T, et al., 2025,
Denoising and iterative phase recovery reveal low-occupancy populations in protein crystals
, Communications Biology, Vol: 8, ISSN: 2399-3642Advances in structural biology increasingly focus on uncovering protein dynamics and transient macromolecular complexes. Such studies require modeling of low-occupancy species like time-evolving intermediates and bound ligands. In protein crystallography, difference maps that compare paired perturbed and reference datasets are a powerful way to identify and aid modeling of low-occupancy species. Current methods to generate difference maps, however, rely on manually tuned parameters and, when signals are weak due to low occupancy, can fail to extract clear, chemically interpretable signals. We address these issues, first by showing that negentropy – a measure of how different a signal looks from anticipated Gaussian noise – is an effective metric to assess difference map quality and can therefore be used to automatically determine difference map calculation parameters. Leveraging this, we apply total variation denoising, an image restoration technique that requires a choice of regularization parameter, to crystallographic difference maps. We show that total variation denoising improves map signal-to-noise and enables us to estimate the latent phase contribution of low-occupancy states. We implement this technology in an open-source Python package, METEOR. METEOR opens new possibilities, for time-resolved and ligand-screening crystallography especially, allowing detection of low-occupancy states that could not previously be resolved.
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Journal articleChen H, Xu Y, Xiong Z, et al., 2025,
Cinnamic-Hydroxamic-Acid Derivatives Exhibit Antibiotic, Anti-Biofilm, and Supercoiling Relaxation Properties by Targeting Bacterial Nucleoid-Associated Protein HU
, ADVANCED SCIENCE -
Journal articleChatzilakou E, Hu Y, Al Musaimi O, et al., 2025,
Peptide-based fluorescent biosensing system for the detection of the melanoma biomarker S100B
, Bioconjugate Chemistry, Vol: 36, Pages: 2357-2369, ISSN: 1043-1802Cutaneous melanoma, responsible for 80% of skin cancer mortality, presents urgent diagnostic challenges due to insufficient early detection methods. Current clinical methods rely on invasive biopsies, while noninvasive approaches primarily serve as adjunctive decision-support tools rather than definitive diagnostics. Here, a peptide-based fluorescent biosensing system was developed for the sensitive and rapid detection of S100B, a key prognostic biomarker for melanoma. Our system employs a fluorescently labeled peptide beacon designed for Förster resonance energy transfer (FRET)-based detection, achieving a subnanomolar detection limit (∼0.045 nM) and great selectivity in human serum samples. Peptide synthesis was performed using optimized solid-phase protocols, enabling precise sequence assembly, while the peptide sensor offers efficient detection, lower costs, and high specificity through tailored peptide–protein interactions. The biosensing probe employs complementary peptide nucleic acid (PNA) interactions to achieve proximity-induced fluorescence quenching in the absence of S100B, which reverses via structural rearrangement upon specific S100B binding for accurate quantification. Computational and experimental optimization of the synthetic process has enhanced binding efficiency, sensitivity, and response time–crucial parameters for melanoma-specific detection. By integrating advanced molecular design with optical biosensing, this mechanism aims to enhance the accuracy and accessibility of melanoma diagnostics, ultimately addressing healthcare disparities and improving patient outcomes.
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Journal articleAhmad Z, Tyagi G, Xiang S, et al., 2025,
Surface wrinkling of plasma-exposed PDMS is caused by water vapor sorption: an optical environmental sensor
, Advanced Functional Materials, Vol: 35, ISSN: 1616-301XWrinkling of polydimethylsiloxane (PDMS) has unlocked a plethora of technological applications, from tunable surface wetting to photonic response. Surface undulations with prescribed wavelength and amplitude are excited by in-plane mechanical compression of bilayers comprising a thin, stiff outer skin on a soft elastomer or gel. Plasma oxidation has become ubiquitous for creating such thin (≈10 nm) glassy interfacial layers. Spontaneous wrinkling can occur even in the absence of external mechanical strain fields, which has been rationalized in terms of a thermally-induced strain that accompanies the expansion-contraction cycle of such laminate films. It is shown that exposure to water vapor is, instead, responsible for surface wrinkling, due to the swelling the oxidized skin layer. This interpretation of surface wrinkling provides a rationale for the apparent experimental variability of the wrinkling process. This hypothesis is verified experimentally by observing and modelling the spatiotemporal evolution of the reversible wrinkling process under a range of controlled environmental conditions. From a practical standpoint, it is found that this effect provides for a facile approach for humidity sensing through structural color changes arising from the diffractive wrinkled skin.
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Journal articlePenadés JR, Gottweis J, He L, et al., 2025,
AI mirrors experimental science to uncover a mechanism of gene transfer crucial to bacterial evolution
, Cell, Vol: 188, Pages: 6654-6665.E2, ISSN: 0092-8674Artificial intelligence (AI) models have been proposed for hypothesis generation, but testing their ability to drive high-impact research is challenging since an AI-generated hypothesis can take decades to validate. Here, we challenge the ability of a recently developed large language model (LLM)-based platform, AI co-scientist, to generate high-level hypotheses by posing a question that took years to resolve experimentally but remained unpublished: how could capsid-forming phage-inducible chromosomal islands (cf-PICIs) spread across bacterial species? Remarkably, the AI co-scientist’s top-ranked hypothesis matched our experimentally confirmed mechanism: cf-PICIs hijack diverse phage tails to expand their host range. We critically assess its five highest-ranked hypotheses, showing that some opened new research avenues in our laboratories. We benchmark its performance against other LLMs and outline best practices for integrating AI into scientific discovery. Our findings suggest that AI can act not just as a tool but as a creative engine, accelerating discovery and reshaping how we generate and test scientific hypotheses.
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Journal articleHe L, Patkowski JB, Wang J, et al., 2025,
Chimeric infective particles expand species boundaries in phage-inducible chromosomal island mobilization
, Cell, Vol: 188, Pages: 6636-6653.E17, ISSN: 0092-8674Some mobile genetic elements spread among unrelated bacterial species through unknown mechanisms. Recently, we discovered that identical capsid-forming phage-inducible chromosomal islands (cf-PICIs), a new family of phage satellites, are present across multiple species and genera, raising questions about their widespread dissemination. Here, we have identified and characterized a new biological entity enabling this transfer. Unlike other satellites, cf-PICIs produce their own capsids and package their DNA, relying solely on phage tails for transfer. cf-PICIs release non-infective, tailless capsids containing their DNA into the environment. These subcellular entities then interact with phage tails from various species, forming chimeric particles that inject DNA into different bacterial species depending on the tail present. Additionally, we elucidated the structure of the tailless cf-PICIs and the mechanism behind their unique capsid formation. Our findings illuminate the mechanisms used by satellites to spread in nature, contributing to bacterial evolution and the emergence of new pathogens.
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Journal articleKoutentaki F, Nicastro L, Kelwick R, et al., 2025,
Investigating the mechanisms of small extracellular vesicles in cardiovascular disease using the living myocardial slice platform
, Frontiers in Cardiovascular Medicine, Vol: 12, ISSN: 2297-055XCardiovascular disease remains the leading cause of death worldwide. Extracellular vesicles (EVs) play a regulatory role in homeostasis, associated with their contribution to cell-cell communication. Recently, it has been confirmed that they also regulate the progression of cardiovascular disease. Specifically, myocardial injury induces an increase in the secretion of small extracellular vesicles (sEVs), both in the cardiac microenvironment and peripheral circulation. Small extracellular vesicles (sEVs) are lipid bilayer particles within the size range of 35-200nm and are secreted by all cell types. Their high content of bioactive cargo – primarily miRNA – is altered in response to external stimuli, leading to behavioral changes of the recipient cells. In the context of cardiovascular disease, this change leads to acute and long term functional, structural, and biochemical effects on the myocardium. However, the mechanism behind the altered sEVs secretion and their changes in content in the context of cardiovascular disease is yet to be determined. That is partially due to the challenges associated with the isolation of cardiac-derived sEVs, which are essential for the investigation of the mechanisms behind cardiovascular disease progression. Living myocardial slices (LMS) provide an ideal platform for the isolation and investigation of sEVs function in the myocardium. Indeed, LMS not only maintain the cellular complexity and architecture of the native adult myocardium but can also be cultured over days/weeks without significant alterations in cardiac function, making them a reliable model for sEVs isolation and characterization at multiple timepoints. This review aims to summarize recent findings on the effect of sEVs on the onset and progression of cardiovascular disease and to discuss different methods for their isolation from LMSs and the investigation of their functional, structural, and biochemical effect on the myocardium.
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Journal articleRochfort Peters GM, Baum J, 2025,
Better late than never: defining the ideal vaccine that targets pre-erythrocytic malaria infection
, EMBO MOLECULAR MEDICINE, Vol: 17, Pages: 2847-2849, ISSN: 1757-4676 -
Journal articleIshimoto N, He S, Bogdanov M, et al., 2025,
Phospholipid-independent biogenesis of a functional RP4 conjugation pilus.
, bioRxivConjugation, the process of DNA transfer between bacteria, is initiated universally by the formation of a mating pair formation (MPF) via a conjugative pilus. Conjugation of the IncP RP4 plasmid is mediated by short, non-retractable, rigid mating pili. Here, we report the cryo-EM structure of the RP4 pilus at 2.75 Å resolution. Uniquely, and consistently with quantitative mass spectral analysis, this revealed that the cyclic TrbC pilin subunit is not lipidated. Consistently, an E. coli pgsA mutant lacking phosphatidylglycerol (PG) can serve as a donor of RP4 but not of R27, encoding the H-pilus consisting of PG-associated cyclic pilin subunits (TrhA). The RP4 is the first example of a lipid-independent functional mating pilus. This discovery not only challenges the long-held assumption that an amphipathic lipid moiety is essential for the construction of conjugative pili and for MPF, but also expanding our understanding of the diverse mechanisms that bacteria employ to transfer genetic material.
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Journal articleWaititu JK, Nilsson K, Larrouy-Maumus G, et al., 2025,
RfaH is essential for virulence and adaptive responses in Yersinia pseudotuberculosis infection
, mBio, Vol: 16, Pages: 1-22, ISSN: 2161-2129We previously suggested that increased expression of the gene encoding transcriptional antiterminator RfaH during Yersinia pseudotuberculosis transcriptional reprogramming is necessary for adapting to persistent infection. In this study, we examined the role of RfaH in virulence and bacterial physiology under infection-relevant stress conditions, and identified genes differentially regulated in the absence of RfaH in Y. pseudotuberculosis. We employed a mouse infection model and phenotypic assays to test RfaH’s role in virulence and physiology, as well as RNA sequencing, including O-antigen biosynthesis-deficient strains. Our findings demonstrate that loss of RfaH significantly attenuates virulence, reducing the capacity of Y. pseudotuberculosis to establish persistent infection. RfaH expression is increased during the stationary growth phase and under various stress conditions, such as high osmolarity and bile salts, which are known to induce envelope stress. Functional assays revealed that the ΔrfaH strain displayed defects in motility and increased clumping, indicating altered surface properties affecting motility. Moreover, transcriptomic profiling of the ΔrfaH strain revealed a specific RfaH-dependent gene set after filtering out genes affected by O-antigen-related mutations, thereby minimizing confounding effects from surface structure alterations. These results suggest that RfaH influences a broader set of virulence and adaptation pathways beyond O-antigen regulation. Collectively, our findings suggest that RfaH is essential for the virulence and adaptive capacity of Y. pseudotuberculosis to colonize the host. This study provides insights into regulatory mechanisms that facilitate bacterial survival in hostile environments and highlights the importance of RfaH and its regulatory targets in the pathogenesis of Y. pseudotuberculosis.
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