Microbiology & Infectious Disease Publications

Adam Evans, Bethan Kelly, Pooja Sridhar, Alice J. Rothnie, Naomi L. Pollock, Philip M. Ireland, David I. Roper, Tim R. Dafforn

Extraction and purification of membrane proteins has for a long time represented a significant challenge. Polymer-based extraction methods, like those using styrene maleic acid co-polymers have provided a fertile approach to generate samples that include the local lipid environment surrounding the protein. However, the wide variety of different polymers now available provides a challenge to identify the optimal solution. In this study we develop and demonstrate a novel high-throughput screening approach for rapid optimization of polymer solubilization agents and chromatography resins for membrane protein purification. Using this approach, we explore whether there are standard conditions that perform well for a range of membrane protein morphologies, sources and functions. These data show that no such standard conditions exist for either polymer solubilization agent or chromatography resin and that some combinations are rarely suitable for membrane protein purifications under these conditions, such as the use of TALON resin at a pH of 7.5 or SMALP300 in the Synthetic Nanodisc Screening Kit MINI kit. Instead, the use of the screening approach developed in this work is the best route to an optimal membrane protein preparation protocol.

Protein Science, January 2026

Joshua Williams, Ioannis P Nezis, Antonia P Sagona

The rising incidence of antimicrobial resistance (AMR) in bacterial infections has strongly necessitated the development and deployment of alternative therapeutics. Bacteriophages (phages) are one such alternative, discovered in the early twentieth century. While a key tool in landmark molecular biology studies throughout the twentieth century, their popularity as an antimicrobial in clinical contexts was largely overshadowed by the development and use of antibiotics. The global threat of AMR has since reignited interest in utilizing phages as therapeutics. A key advantage of phages is their genetic tractability, allowing for the generation of a cornucopia of derivatives armed with numerous exogenous functions depending on the end use. A nascent yet growing interest in this field is the arming of phages for direct and selective human tissue entry to eradicate intracellular bacterial infections, where many bacterial species exert their pathogenesis. Engineering phages in such a way also opens opportunities to study the complex, multilayered cellular mechanisms behind phage–eukaryote interactions. In this review, we discuss the progress of phage genetic engineering with an emphasis on phage–eukaryote interactions and how knowledge of the underlying molecular mechanisms may serve further development of this prospective enhancement of engineered phages.

Current Opinion in Microbiology, February 2026

Gbeminiyi J. Oyedele, Ankit Shanker, Michael J. Tildesley, Ivo Vlaev

Adherence to self-isolation was a central measure for controlling the spread of COVID-19; however, compliance varied widely. Understanding the behavioural determinants that drive adherence is critical for informing future public health intervention. This study applied the COM-B model to examine the associations between capability, opportunity, motivation, and self-isolation behaviour during the COVID-19 pandemic in the United Kingdom. A retrospective analysis was conducted using secondary data from the UK Office for National Statistics 2019 Opinions and Lifestyle Survey, which was not originally designed to measure COM-B constructs. Structural equation modelling (SEM) was used to examine the relationships between capability, opportunity, motivation, and self-isolation behaviour. Opportunity and motivation were significantly associated with self-isolation, while capability was linked to behaviour indirectly through its association with motivation, reflecting a possible pathway suggested by the structural model. Although some measurement indicators demonstrated lower reliability owing to the use of secondary data, the overall model fit was good (RMSEA = 0.049, CFI = 0.966, TLI = 0.944, SRMR = 0.040). These findings highlight the dominant influence of social and motivational factors in shaping adherence. This study demonstrates the utility of the COM-B model for understanding self-isolation behaviour despite the constraints of secondary data. The findings highlight opportunity and motivation as key levers for promoting adherence and offer actionable insights for policymakers to design interventions that enhance motivation, strengthen social support, and sustain compliance during future public health emergencies.

Scientific Reports, January 2026

Steven Xingyu Wu, Christopher N. Davis,Mark Arnold, Michael J. Tildesley

Previous research efforts on highly pathogenic H5N1 avian influenza (HPAI) suggest that different avian species exhibit a varied severity of clinical signs after infection. Waterfowl, such as ducks or geese, can be asymptomatic and act as silent carriers of H5N1, making detection harder and increasing the risk of further transmission, potentially leading to significant economic losses. For backyard hobby farmers, passive reporting is a common HPAI detection strategy. We aim to develop a computational, mechanistic model to quantify the effectiveness of this strategy by simulating the spread of H5N1 in a mixed-species, small-population backyard flock. Quantities such as detection time and undetected burden of infection in various scenarios are compared. Our results indicate that the presence of ducks can lead to a higher risk of an outbreak and a higher burden of infection. If most ducks within a flock are resistant to H5N1, detection can be significantly delayed. We find that within-flock infection dynamics can heavily depend on the species composition in backyard farms. Ducks, in particular, can pose a higher risk of transmission within a flock or between flocks. Our findings can help inform surveillance and intervention strategies at the flock and local levels.

PLOS Computational Biology, January 2026

Christopher N. Davis, Edward M. Hill, Chris P. Jewell, Kristyna Rysava, Robin N. Thompson, Michael J. Tildesley

Since 2020, large-scale outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in Great Britain have resulted in substantial poultry mortality and economic losses. Alongside the costs, the risk of circulation leading to a viral reassortment that causes zoonotic spillover raises additional concerns. However, the precise mechanisms driving transmission between poultry premises and the impact of potential control measures in Great Britain, such as vaccination, are not fully understood. We have developed a spatial transmission model for the spread of HPAI in poultry premises calibrated to infected premises data for the 2022–23 season using Markov chain Monte Carlo. Our results indicate that reducing the susceptibility of the premises surrounding an identified infected premises (for example, through enhanced biosecurity measures and/or vaccination) can substantially reduce the overall number of infected premises. Our findings highlight that enhanced control measures could limit the future impact of HPAI on the poultry industry and reduce the risk of broader health threats.

PLOS Computational Biology, January 2026

Nikhil Bhalla, Mojgan Rabiey, Prachi Bendale, Katie Lawther, Janice Spencer, Alberto Longo, Lucky Lucky, Vishal Chaudhary, Paul McCormack, Saikat Jana, Patrick S. M. Dunlop, Linda Oyama

Antimicrobial resistance (AMR) is a silent pandemic that presents a global challenge, urging researchers to develop innovative and transdisciplinary solutions. Our initiative aims to promote collaboration across science, engineering, economics, social sciences, and the arts to address the complex dimensions of AMR. We highlight the unique role of early-career researchers (ECRs) in advancing such cross-cutting approaches and conclude that empowering ECRs through equitable support and recognition is essential to sustaining innovation and mobilising communities against AMR.

Nature Communications, January 2026

E. Burton, S.P. Borriello, P.J. Gregory, J. Healing, C. Nicholson, T.H. Oliver, S. Pearson, R. Smith, M. Tildesley, J. Wastling, J. O'Brien

Establishing research priorities to support evidence-based regulatory goals requires cross disciplinary collective expert input. This paper reviews the application of expert elicitation to identify and prioritize research questions in food safety regulation, which approach offers regulators and research funders a rapid, reliable, and cost-effective method for assessing evidence gaps in an expanding scientific landscape. While similar methodologies have been applied in ecology and other fields, this is, to our knowledge, the first use in food safety research. Recommendations are provided to strengthen the process.

A facilitated workshop shortlisted 51 questions, grouped into 12 themes, from a long list of 262 submissions, which spanned broad topics, including understanding the origins of emerging hazards and their health impacts. Environmental and sustainability themes address unintended consequences of decarbonization, food waste reduction, and risks from recycled plastics and food byproducts. Dietary change raises questions on emerging allergens, nutritional adequacy of alternative proteins, low fibre intake, and microbiome-related health impacts. Technology-driven changes, such as new production systems, kitchen devices, and secondary food economies, intersect with these dietary shifts.

Scientific advances provide opportunities to improve understanding of the dietary exposome through better intake data. Exposure to dietary chemicals occurs alongside complex mixtures of other agents, requiring structured approaches to risk assessment. The evolving science of chemical mixtures and rapid innovation in food systems underscore the need for robust, prioritized research compatible with good regulatory practice.

Trends in Food Science & Technology, January 2026

Hugo Millat, Cassandra Falcou, Cassandra Lenoir, Nicholas S. Briggs, Jack Stone, Pierre Simon Garcia, Sylvie Manuse, Caroline Cluzel, André Zapun, Cécile Morlot, David I. Roper, Adrien Ducret, Christophe Grangeasse

Class A penicillin-binding proteins (aPBPs) are involved in the biosynthesis and remodelling of peptidoglycan (PG). The human bacterial pathogen Streptococcus pneumoniae produces three aPBPs, which are regulated to maintain the bacterium’s ovoid shape. Evidence suggests that PBP1a and PBP2a activities are closely coordinated; however, their precise functions remain unclear. Here we characterized the pneumococcal S protein, which contains a LysM-PG-binding domain and a GpsB-interacting domain. Using S protein fusion constructs or mutant bacterial strains, we show that S protein localizes to the division ring and is required to prevent premature cell lysis and minicell formation due to aberrant division site placement. S protein interacts with PBP1a and activates its PG synthesis activity. Co-immunoprecipitation experiments combined with biochemical, genetic, structural prediction and microscopy analyses suggest that S protein is part of a larger multiprotein complex containing aPBPs and PG-modifying enzymes, and coordinated by the scaffolding protein GpsB. Together, these findings suggest that a GpsB-associated complex orchestrates PG biosynthesis and remodelling in S. pneumoniae.

Nature Microbiology, January 2026

Emma L. Fairbanks, Matthew Baylis, Janet M. Daly, Michael J. Tildesley

Vector-borne disease transmission involves complex interactions between vectors, reservoir hosts and dead-end hosts. We present a mathematical model for the vectorial capacity that incorporates multiple host types and their interactions, focusing specifically on West Nile virus transmission by Culex pipiens mosquitoes. Our model integrates climate-dependent parameters affecting vector biology with vector control interventions to predict transmission potential under various scenarios. We demonstrate how vector control interventions targeting one host type can significantly impact transmission dynamics across all host populations. By examining the effects of different vector control tool modes of action (repellency, preprandial killing, disarming and postprandial killing), we develop target product profiles that minimise unintended consequences of vector control. Notably, we identify the optimal intervention characteristics needed to prevent repellency on dead-end hosts from inadvertently increasing transmission among reservoir hosts. This research provides valuable insights for public health officials designing targeted vector control strategies and offers a flexible modelling framework that can be adapted to other vector-borne diseases with complex host dynamics.

PLOS Computational Biology, December 2025

Matthew Adeoye, Xavier Didelot, Simon E.F. Spencer

The Bayesian analysis of infectious disease surveillance data from multiple locations typically involves building and fitting a spatio-temporal model of how the disease spreads in the structured population. Here we present new generally applicable methodology to perform this task. We introduce a parsimonious representation of seasonality and a biologically informed specification of the outbreak component to avoid parameter identifiability issues. We develop a computationally efficient Bayesian inference methodology for the proposed models, including techniques to detect outbreaks by computing marginal posterior probabilities at each spatial location and time point. We show that it is possible to efficiently integrate out the discrete parameters associated with outbreak states, enabling the use of dynamic Hamiltonian Monte Carlo (HMC) as a complementary alternative to a hybrid Markov chain Monte Carlo (MCMC) algorithm. Furthermore, we introduce a robust Bayesian model comparison framework based on importance sampling to approximate model evidence in high-dimensional space. The performance of our methodology is validated through systematic simulation studies, where simulated outbreaks were successfully detected, and our model comparison strategy demonstrates strong reliability. We also apply our new methodology to monthly incidence data on invasive meningococcal disease from 28 European countries. The results highlight outbreaks across multiple countries and months, with model comparison analysis showing that the new specification outperforms previous approaches.

Epidemics, December 2025

Fatima Ulhuq, Amy K. Tooke, Chriselle Mendonca​, Guillermina Casabona​, Johann Habersetzer​, Yaping Yang​, Margarida C. Gomes, Felicity Alcock​, Serge Mostowy​, Tracy Palmer

The Staphylococcus aureus type VIIb secretion system (T7SSb) is a multiprotein secretion system that secretes toxins with antibacterial activity, but which is also required for full virulence in animal models of infection. S. aureus strains carry one of four T7SSb locus types, named essC1 to essC4, each of which encodes a characteristic LXG-family substrate at the T7SS locus. In essC2 strains, this LXG-domain protein is EsxX, which has a glycine zipper sequence in its C-terminus and has potent antibacterial, membrane-depolarizing activity. In this work, we recognize conserved features of the essC2 and essC3 systems, identifying the LXG protein SAR0287 as structurally and functionally similar to EsxX. Using a zebrafish larval hindbrain ventricle infection model, we demonstrate that the T7SSb of essC2 and essC3 representative strains contributes to bacterial replication and zebrafish mortality. However, there is no significant loss of virulence in the model system if EsxX or SAR0287 is absent. These findings indicate that there is no discernible role for either toxin in this virulence model.

Microbiology, December 2025

Ning Wang, Linda M. Westermann, Mingyu Li, Chun-Yang Li, Andrew R. J. Murphy, Zengtian Gu, Eleonora Silvano, Claudia A. Blindauer, Ian D. E. A., Yu-Zhong Zhang, David J. Scanlan, Yin Chen

All cells use lipid membranes to maintain cellular integrity and function, though Archaea utilize lipids composed of glycerol-1-phosphate (G1P), while Bacteria and Eukaryotes use glycerol-3-phosphate (G3P). Given that Archaea contribute significantly to global marine biomass, accounting for 0.3 gigatonnes (Gt) of carbon in the oceans, we aimed to uncover how archaeal G1P is recycled by marine microorganisms. Through a multidisciplinary approach combining microbiology, biochemistry, and structural biology, we identified a G1P transporter in marine bacteria, which we named GpxB. Phylogenetic analysis revealed that GpxB belongs to the organic phosphonate transporter (PhnT) family and is widely distributed in the marine microbiome, found in approximately 5 to 10% of microbial cells in surface marine waters. Strikingly, we also identified a second G1P transporter, UgpB, that is known to transport G3P and belongs to the carbohydrate uptake transporter-1 (CUT1) family, in the model bacterium Phaeobacter sp. MED193. To explore the evolutionary pathways that led to the formation of G1P binding sites in both the PhnT and CUT1 families, we determined the structures of GpxB and UgpB bound to G1P and G3P. Using structure-guided mutagenesis and a comparative analysis of the binding pockets within the PhnT and CUT1 families, we traced their evolutionary trajectories, highlighting the distinct strategies through which G1P-binding sites developed in these two protein families.

PNAS, December 2025

Yayoi Sugita, Amanda J. Dowson, Ichiro Kajisa, Katsuaki Takechi, Yilan E, Jingzhi Zhao, Jiaqi Wang, Xiaofei Lin, Laura Diaz-Saez, Adrian J. Lloyd, Christopher G. Dowson, Hiroyoshi Takano

It is understood that a cyanobacterium was the progenitor of plastids and that the biosynthesis of cell wall peptidoglycan was lost during chloroplast evolution. However, accumulated data, especially from the moss Physcomitrium patens, suggest that peptidoglycan remains essential for plastid division in some land plants. A fundamental set of peptidoglycan biosynthesis (Mur) genes has been identified in the genomes of these land plants, while many angiosperms no longer encode some core Mur genes, including a bifunctional penicillin-binding protein (PBP). Ten incomplete Mur genes were previously identified in the genome of the gymnosperm Picea abies but these could be pseudogenes or encode proteins that have been repurposed. For instance, mutant albino maize and Arabidopsis seedlings possess a defective UDP-N-acetylmuramoyl-l-alanyl-d-glutamate--2,6-diaminopimelate ligase (MurE), an intact MurE ligase being essential for peptidoglycan synthesis. In this study, we isolated a full set of cDNAs for peptidoglycan biosynthesis from P. abies. GFP fusion proteins with either P. abies (Pa)MurE or PaPBP were detected in chloroplasts. Cross-species complementation assays with PaMurE in Arabidopsis albino MurE mutants and Physcomitrium MurE chloroplast division mutants showed that the gymnosperm MurE completely rescued both mutant phenotypes. Enzymatic assay of recombinant PaMurE proteins revealed they catalyze the same reaction performed by their bacterial MurE homologs. Moreover, the expression of the PaPbp cDNA partially rescued the giant chloroplast phenotype in the moss Pbp knockout line. These results are consistent with the operation of a functional Mur gene set in the Norway spruce genome.

The plant Journal, December 2025

European Food Safety Authority (EFSA), Elena Lázaro, Stephen Parnell, Antonio Vicent Civera, Martijn Schenk, Jose Cortiñas Abrahantes, Juan Navas-Cortes, Hans-Hermann Thulke, Francesco Pecori, Joshua Koh, Jan Schans, Marc Aerts, Gabriele Zancanaro, Sybren Vos, Tomasz Kaluski

At the request of the European Commission, EFSA prepared the general guidelines for surveys of plant pests, describing the legal, international and scientific context in which the surveys are designed, the basic principles implemented for surveillance of quarantine pests and introducing the concepts needed for the design of statistically sound and risk-based surveys. Three types of specific surveys are addressed: detection surveys for substantiation of pest freedom, delimiting surveys to determine the boundaries of a potential infested zone, and monitoring surveys for prevalence estimation when measuring the effectiveness of eradication measures or for the confirmation of a low pest prevalence area. For each type of survey, the survey parameters are introduced and their interactions analysed showing the importance of the assumptions that are taken for each one of them:

1) The aims of the survey are defined as achieving a certain level of confidence of detecting a given pest prevalence (design prevalence), this reflects the trade-off between the acceptable level of the risk and availability of resources that determine the strength of the evidence to support the conclusion of the survey;

2) The target population is described by its structure and size, including the risk factors; and

3) The method sensitivity is defined as the combination of the sampling effectiveness and the diagnostic sensitivity for each inspection unit. EFSA's RiPEST and RiBESS+ tools1 are introduced for calculating the sample size using the survey parameters as input values for a statistically sound and risk-based survey design. The mathematical principles behind the tools are in line with the International Standards for Phytosanitary Measures. The survey design is flexible and can be tailored to each pest and specific situation in the Member States. Once the survey is implemented following this approach, the conclusions allow surveys to be compared across time and space, contributing to the harmonisation of surveillance activities across the EU Member States.

EFSA Supporting Publications, December 2025

Alicia Gill, Jere Koskela, Xavier Didelot, Richard G Everitt

Inference of the reproduction number through time is of vital importance during an epidemic outbreak. Typically, epidemiologists tackle this using observed prevalence or incidence data. However, prevalence and incidence data alone are often noisy or partial. Models can also have identifiability issues with determining whether a large amount of a small epidemic or a small amount of a large epidemic has been observed. Sequencing data however are becoming more abundant, so approaches which can incorporate genetic data are an active area of research. We propose using particle MCMC methods to infer the time-varying reproduction number from a combination of prevalence data reported at a set of discrete times and a dated phylogeny reconstructed from sequences. We validate our approach on simulated epidemics with a variety of scenarios. We then apply the method to real datasets of HIV-1 in North Carolina, USA and tuberculosis in Buenos Aires, Argentina. The models and algorithms are implemented in an open source R package called EpiSky which is available at https://github.com/alicia-gill/EpiSkyLink opens in a new window.

Journal of the Royal Statistical Society Series C (Applied Statistics), December 2025

Nabil Karah, Nathan Faille​, Nancy Allard, Frédéric Grenier, Antoine Abou-Fayad, Paul G. Higgins, Leena Al-Hassan, Benjamin A. Evans, Laurent Poirel, Rémy A. Bonnin, Anette M. Hammerum, Frank Hansen, Rayane Rafei, Monzer Hamze, Xavier Didelot, Santiago Castillo-Ramírez, Simon Lévesque, Sébastien Rodrigue, Bernt Eric Uhlin, Louis-Patrick Haraoui

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are of great concern, as mortality is high, and treatment options are very limited. Despite having among the highest rates reported worldwide, scarce genomic data are available on CRAB strains from the Middle East. Here, we report the global emergence of a novel International Clone (IC), designated IC12, based on the epidemiological, phenotypic and genome sequencing data (short reads and long reads) of a set of 60 A. baumannii isolates belonging to multilocus sequence type 158 (Pasteur scheme). IC12, prevailing in the Middle East since 2007, has also been found in Europe, Asia and South America. Alleles OXA-65 and ADC-117, coded by the blaOXA-51-like and blaADC A. baumannii-intrinsic genes, respectively, were hallmarks shared by all the isolates. Plasmid pIC12-2 (80,000 bp), which carries a repAci6 replication initiator (RP-T1) and a type IV conjugative transfer system, played a major role in the antimicrobial resistance profile of 54/60 of the IC12 isolates. This resistance was mediated by three mobile genetic elements, namely Tn2008, MITEAb-IC12 and TnaphA6. All four Peruvian IC12 isolates lacked pIC12-2 and carried a different set of plasmids. Two of the Peruvian isolates carried a chromosomal resistance island of 79,396 bp long (designated IC12-RI) marked by the occurrence of tet(X3). The global spread of IC12 is worrying and calls for further studies on the virulence features and clinical impact of this clone.

Microbial Genomics, November 2025

Chao Yan,Shanwei Tong, Yarong Wu, Yujie Chen,Xinyu Jia,Yan Guo,Mengnan Cui,Guangqian Pei, Zuming Zhang, Hao Zhou, BAdmin , Kai Mu,Xue Ren,Bing Du, Hanqing Zhao,Yanling Feng,Jinghua Cui,Yuyan Xia, MBBS , Zhen Wang, Yu Sun,Prof Linqing Zhao, Prof Chuangli Hao, Zhijie Zhu, Shengqiang Luo, Han Zhang, Yongjun Wang , Prof Lili Zhong, DehuiChen , Prof Yong Yin , Longji Hu, Prof Yuehua Ke, Prof Guanhua Xue, Prof Ling Cao, , Prof Xavier Didelot, Prof Jing Yuan, Prof Yujun Cui,

Background: After a prolonged period of low detection rates, Mycoplasma pneumoniae resurged in China, during September to November, 2023, raising global concern. This study aims to gain a better understanding of the genetic mechanisms underlying the 2023 increase in cases and the evolutionary dynamics of the epidemic populations, which has been previously hampered due to limited genomic data of this pathogen.

Methods: We sequenced 685 M pneumoniae isolates, including 248 isolates from 11 Chinese provinces and municipalities in 2023 and 437 isolates from Beijing (2013–22). By analysing these isolates and 436 publicly global sequences, we reconstructed the pathogen’s evolutionary history using time-calibrated phylogenies and effective population size inference. We investigated potential genomic variations contributing to the 2023 resurgence through genome-wide association study and conducted phylogeographic analysis of the 2023 isolates across China.

Findings: Two macrolide-resistant epidemic clusters (T1-2-EC1 and T2-2-EC2) were responsible for the 2023 resurgence in China. Both clusters, having acquired the 23S ribosomal RNA A2063G mutation conferring macrolide resistance, emerged in approximately 1997 and 2014, respectively, and subsequently outcompeted their predecessor populations. This coincided with China’s large-scale adoption of azithromycin for paediatric community-acquired pneumonia around the early 2000s. Aside from macrolide resistance, T1-2-EC1 independently acquired 17 clade-specific mutations and T2-2-EC2 four clade-specific mutations, which could further explain their increased competitiveness. Whole-genome analysis revealed no resurgence-specific mutations in the 2023 isolates. Phylogeographic analysis showed rapid mixing of T1-2-EC1 isolates between different sampled regions within China.

Interpretation: Our study provides evidence that the 2023 resurgence in China is a continuation of the pre-COVID epidemic, rather than emergence of novel variants. The high prevalence of macrolide resistance and rapid intranational spread emphasise the urgent need for enhanced global surveillance of this pathogen.

The Lancet (Microbe), December 2025

Kandas Traore, Damien Seyer, Agnes Mihajlovski, Antonia P Sagona

Antimicrobial resistance represents one of the most serious threats to both public health and economic sustainability. One of the promising approaches to address this problem is phage therapy – treatment of pathogenic bacterial infections using bacteriophages. Bacteriophages have a narrow host spectrum of activity, minimal side effects and self-replication at the infection site, which positions them as promising candidates to complement or replace conventional antibiotics. Moreover, they can be easily genetically modified to enhance their effectiveness and safety. In this At a Glance article, we highlight the timely relevance of engineered phages as an innovative solution in a rapidly evolving healthcare landscape. First, we introduce bacteriophages' life cycle, ecology and therapeutic history, emphasizing their role in One Health strategies. Then, we describe advanced engineering techniques that can be used to expand bacteriophages' functionalities. Finally, we discuss innovative applications of engineered bacteriophages in biotechnological applications and as a potential countermeasure for antimicrobial resistance, including serving as a shuttle for delivering genes and drugs to the targeted bacterial and eukaryotic cells, targeting intracellular bacteria, contributing to vaccine development, facilitating advancements in tissue engineering and improving bacteriophages' antibacterial properties.

Disease Models and Mechanisms, September 2025

Matt Combes, Nathan Brown, Robin N. Thompson, Alexander Mastin, Peter Crow, Stephen Parnell

Invasive plant pests and pathogens cause substantial environmental and economic damage. Visual inspection remains a central tenet of plant health surveys, but its sensitivity (probability of correctly identifying the presence of a pest) and specificity (probability of correctly identifying the absence of a pest) are not routinely quantified. As knowing sensitivity and specificity of visual inspection is critical for effective contingency planning and outbreak management, we address this deficiency using empirical data and statistical analyses. Twenty-three citizen scientist surveyors assessed up to 175 labelled oak trees for three symptoms of acute oak decline. The same trees were also assessed by an expert who has monitored these individual trees annually for over a decade. The sensitivity and specificity of surveyors was calculated using the expert data as the ‘gold-standard’ (i.e., assuming perfect sensitivity and specificity). The utility of an approach using Bayesian modelling to estimate the sensitivity and specificity of visual inspection in the absence of a rarely available ‘gold-standard’ dataset was then examined with simulated plant health survey datasets. There was large variation in sensitivity and specificity between surveyors and between different symptoms, although the sensitivity of detecting a symptom was positively related to the frequency of the symptom on a tree. By leveraging surveyor observations of two symptoms from a minimum of 80 trees on two sites, with reliable prior knowledge of sites with a higher (~0.6) and lower (~0.3) true disease prevalence we show that sensitivity and specificity can be estimated without ‘gold-standard’ data using Bayesian modelling. We highlight that sensitivity and specificity will depend on the symptoms of a pest or disease, the individual surveyor, and the survey protocol. This has consequences for how surveys are designed to detect and monitor outbreaks, as well as the interpretation of survey data that is used to inform outbreak management.

PLOS - Computational Biology, November 2025

Shannon F. Greer, Sneha Chakravorty, Kieran Cooney-Nutley, Dave Chandler*, Gregory Firth, Rajesh Odedra, Mojgan Rabiey

Bacteriophages, phages or viruses that specifically infect bacteria, have shown promise for the biocontrol of bacterial plant diseases. However, one of the main challenges of using phages in agricultural systems is their precision application, being able to deliver an effective dose to the site of bacterial infection. In this study, a series of artificial and real cherry flower experiments was conducted to test whether commercially managed bumblebees (Bombus terrestris audax) could deliver phage effective against the cherry canker pathogen Pseudomonas syringae pv. syringae (Pss). Freeze-dried phage powder was formulated with powdered-skimmed milk and when tested, was found to retain viability for seven days in artificial bee feed after storage at 4 °C, room temperature or under glasshouse conditions. In both artificial and cherry flower experiments, bees successfully transferred the formulated phage from their hive to up to 88 % of flowers, resulting in significant reduction in Pss populations. Bees were also able to transfer phage between cherry flowers. The application of phages disrupted the cycle of Pss transmission by bees. These results highlight the potential of bee-mediated phage delivery as an effective biocontrol strategy against floral pathogens like Pss.

Biological Control, December 2025

Anna Lazar, Fabrizio Alberti, George Muscatt, Ryan M. Mushinski, Christopher Quince, Gary D. Bending

Background: Tetracladium spp. represent a group of fungi that inhabit various ecological niches, including soil and aquatic environments, where they are considered to have a saprotrophic lifestyle and within plant roots as endophytes. To date, a lack of sequenced Tetracladium spp. genomes has inhibited our understanding of their metabolic potential and ecological interactions. In this study, we aimed to elucidate the genetic differences between aquatic saprotrophic and endophytic strains of Tetracladium spp. by sequencing and analysing the genomes of T. maxilliforme (isolated from Brassica napus roots) and T. marchalianum (isolated from freshwater), alongside 41 publicly available saprotrophic and endophytic Ascomycetes.

Results: Genomic sequencing revealed that T. maxilliforme possesses a genome size of 35.5 Mbp with 9657 predicted genes, while T. marchalianum has a genome size of 33.2 Mbp with 15,230 predicted genes. Our analyses primarily focused on carbohydrate-active enzymes (CAZymes). Both genomes possessed the full range of enzymatic machinery for cellulose degradation, as well as the complete repertoire of genes necessary to degrade plant cell walls. Notably, the genomes lacked essential enzymes for lignin degradation or modification. Furthermore, we observed a complete repertoire of known fungal chitin-degrading enzymes in both genomes, which might be related to potential interactions with other fungi. Enzyme composition profiles revealed distinct groupings, with T. maxilliforme primarily clustering with endophytic or ecologically versatile species, while T. marchalianum was predominantly associated with saprotrophic species. We also identified secondary metabolite biosynthetic gene clusters in both genomes, including several that showed high homology to those of known bioactive compounds.

Conclusions: In summary, our findings offer valuable insights into the genomic adaptations of Tetracladium spp. to various ecological niches, highlighting their enzymatic capabilities for carbohydrate degradation and potential interactions within fungal communities.

BMC Genomics, November 2025

George W Sundin, Sara M Villani, Quan Zeng, Michelle Hulin, Mojgan Rabiey, Kerik Cox

Bacteriophages are viruses capable of infecting bacterial cells. Lytic phages, which infect and kill bacterial cells, are of interest in disease management in human, animal, and plant systems. In plant pathology, the biocontrol of bacterial diseases is of heightened interest because of the lack of efficacious options in many pathosystems. Numerous papers have been published in the past few decades on phage that target plant pathogenic bacteria, and a large majority of these have been focused on phage isolation and characteristics that highlight the promise and potential of phage as biocontrol agents. In contrast, relatively few of these papers have reported results from studies conducted in the field. Of the recent papers (2022 to 2025) reporting field studies, disease efficacy results are inconsistent. We argue that field studies should be an essential component of phage biocontrol research to understand how to best utilize and deploy phages to generate consistently effective disease management.

Plant Disease, November 2025.

Marina Romanello, Maria Walawender, Shih-Che Hsu, Annalyse Moskeland, Yasna Palmeiro-Silva, Daniel Scamman, James W Smallcombe, Sabah Abdullah, Melanie Ades, Abdullah Al-Maruf, Nadia Ameli, Denitsa Angelova, Sonja Ayeb-Karlsson, Joan Ballester, Xavier Basagaña, Hannah Bechara, Paul J Beggs, Wenjia Cai, Diarmid Campbell-Lendrum, Gina E C Charnley, Orin Courtenay, Troy J Cross, Carole Dalin, Niheer Dasandi, Shouro Dasgupta, Michael Davies, Matthew Eckelman, Chris Freyberg, Paulina Garcia Corral, Olga Gasparyan, Joseph Giguere, Georgiana Gordon-Strachan, Sophie Gumy, Samuel H Gunther, Ian Hamilton, Yun Hang, Risto Hänninen, Stella Hartinger, Kehan He, Julian Heidecke, Jeremy J Hess, Slava Jankin, Ollie Jay, Dafni Kalatzi Pantera, Ilan Kelman, Harry Kennard, Gregor Kiesewetter, Patrick Kinney, Dominic Kniveton, Vally Koubi, Rostislav Kouznetsov, Pete Lampard, Jason K W Lee, Bruno Lemke, Bo Li, Andrew Linke, Yang Liu, Zhao Liu, Rachel Lowe , Siqi Ma, Tafadzwanashe Mabhaudhi, Carla Maia, Anil Markandya, Greta Martin, Jaime Martinez-Urtaza, Mark Maslin, Lucy McAllister, Celia McMichael, Zhifu Mi, James Milner, Kelton Minor, Jan Minx, Nahid Mohajeri, Natalie C Momen, Maziar Moradi-Lakeh, Karyn Morrisey, Simon Munzert, Kris A Murray, Nick Obradovich, Papa Orgen, Matthias Otto, Fereidoon Owfi, Olivia L Pearman, Frank Pega, Andrew J Pershing, Ana-Catarina Pinho-Gomes, Jamie Ponmattam, Mahnaz Rabbaniha, Tim Repke, Jorge Roa, Elizabeth Robinson, Joacim Rocklöv, David Rojas-Rueda, Jorge Ruiz-Cabrejos, Matilde Rusticucci, Renee N Salas, Adrià San José Plana, Jan C Semenza, Jodi D Sherman, Joy Shumake-Guillemot, Pratik Singh, Henrik Sjödin, Matthew R Smith, Mikhail Sofiev, Cecilia Sorensen, Marco Springmann, Jennifer D Stowell, Meisam Tabatabaei, Federico Tartarini, Jonathon Taylor, Cathryn Tonne, Marina Treskova, Joaquin A Trinanes, Andreas Uppstu, Nicolas Valdes-Ortega, Fabian Wagner, Nick Watts, Hannah Whitcombe, Richard Wood, Pu Yang, Ying Zhang, Shaohui Zhang, Chi Zhang, Shihui Zhang, Qiao Zhu, Peng Gong, Hugh Montgomery, Anthony Costello

Driven by human-caused greenhouse gas emissions, climate change is increasingly claiming lives and harming people's health worldwide. Mean annual temperatures exceeded 1·5°C above those of pre-industrial times for the first time in 2024. Despite ever more urgent calls to tackle climate change, greenhouse gas emissions rose to record levels that same year. Climate change is increasingly destabilising the planetary systems and environmental conditions on which human life depends.

The Lancet, October 2025

McAndrew, Martin B. L., Cook, Jonathan P., Gill, Amy, Sahoo, Kavya, Thomas, Clare, Stansfeld, Phillip J. and Crow, Allister

Type VII ABC transporters are ATP-powered membrane protein complexes that drive key biological processes in the bacterial cell envelope. In Escherichia coli, three of the four Type VII ABC systems have been extensively characterized, including: the FtsEX-EnvC cell division complex, the LolCDE-LolA lipoprotein trafficking machinery, and the MacAB-TolC efflux pump. Here we describe a fourth E. coli Type VII ABC system, YbbAP-TesA, which combines a Type VII ABC transporter with a multifunctional hydrolytic enzyme. Structures of the complete YbbAP-TesA complex, and of YbbAP with and without bound ATP analogues, capture implied long-range transmembrane conformational changes that are the hallmark of this ABC superfamily’s mechanotransmission mechanism. We further show that YbbAP-TesA can hydrolyze a variety of ester and thioester substrates and experimentally confirm a constellation of active site residues in TesA. Our data suggests YbbAP has a role in extracting hydrophobic molecules from the inner membrane and presenting these to TesA for hydrolysis. The work extends collective knowledge of the remarkable diversity of the ABC superfamily and establishes a new function for Type VII ABC transporters in bacterial cells.

PLOS Biology, November 2025

Naomi S. Prosser, Eamonn Ferguson, Jasmeet Kaler, Edward M. Hill, Michael J. Tildesley, Matt J. Keeling, Martin J. Green

BACKGROUND: Psychosocial factors are important for the uptake of livestock disease control measures by farmers and can differ by region, which would have implications for disease control nationally.

METHODS: We investigated altruism, trust, psychological proximity and the COM-B behaviour change framework in a survey of 475 British cattle farmers in 2020. Using regression models, we studied associations between the country farmers lived in and psychosocial and behaviour change factors. RESULTS: There were many between-country differences in farmers' psychosocial and COM-B profiles. Accounting for multiple tests, Scottish cattle farmers reported higher trust in governmental judgements for disease control and greater social opportunity to control disease than English cattle farmers.

LIMITATIONS: There were relatively low numbers of respondents from Scotland and Wales. As such, the results should be interpreted with caution. Northern Irish farmers could not be included in the analyses as there were too few responses.

CONCLUSION: Cattle farmers differed in their psychosocial profiles by country. Our sample of Scottish farmers reported higher trust in, and felt better supported by, government in the context of disease control than the English farmers, which could be due to different disease control approaches between devolved governments. Understanding between-country differences in farmer psychosocial attributes has implications for animal health governance and approaches to disease control.

Veterinary Record, October 2025

Leila T. Alexander, Océane M. Follonier, Andriy Kryshtafovych,| Kim Abesamis, Sabrina Bibi-Triki, Henry G. Box, Cécile Breyton, Françoise Bringel, Loic Carrique, Alessio d'Acapito, Gang Dong, Rebecca DuBois, Deborah Fass, JulianaMartinez Fiesco, Daniel R. Fox, Jonathan M. Grimes, Rhys Grinter, Matthew Jenkins, Roman Kamyshinsky, Jeremy R. Keown, Gerald Lackner, Michael Lammers, Shiheng Liu, Andrew L. Lovering,Tomas Malinauskas, Benoît Masquida, Gottfried J. Palm, Christian Siebold,Tiantian Su, Ping Zhang, Z. Hong Zhou, Krzysztof Fidelis, Maya Topf, John Moult, Torsten Schwed

This article presents an in-depth analysis of selected CASP16 targets, with a focus on their biological and functional significance. The authors highlight the most relevant features of the target proteins and discuss how well these were reproduced in the submitted predictions. While the overall performance of structure prediction methods remains impressive, challenges persist, particularly in modeling rare structural motifs, flexible regions, small molecule interactions, posttranslational modifications, and biologically important interfaces. Addressing these limitations can strengthen the role of structure prediction in complementing experimental efforts and advancing both basic research and biomedical applications.

Proteins (Structure, Function, Bioinformatics), October 2025

Will Scott, Esther Ivorra-Molla, Dipayan Akhuli, Teresa Massam-Wu, Pawel K. Lysyganicz, Rylie Walsh, Matthew Parent, Jonathan Cook, Lijiang Song, Abhishek Kumar, Falk Schneider, Masanori Mishima, Allister Crow, Mohan K. Balasubramanian

Photobleaching of fluorescent proteins often limits the acquisition of high-quality images in microscopy. StayGold, a novel dimeric GFP recently monomerized through sequence engineering, addresses this challenge with its high photostability. There is now a focus on producing different colored StayGold derivatives to facilitate concurrent tagging of multiple targets. The unnatural amino acid 3-aminotyrosine has previously been shown to redshift superfolder GFP upon incorporation into its chromophore via genetic code expansion. Here, we apply the same strategy to redshift StayGold through substitution of tyrosine-58 with 3-aminotyrosine. The resultant red fluorescent protein, StayRose, shows an excitation wavelength maximum of 530 nm and an emission wavelength maximum of 588 nm. Importantly, the monomeric mStayRose retains the favorable photostability in vivo in Escherichia coli and zebrafish embryos. A high-resolution crystal structure of StayRose confirms the modified structure of the amino chromophore within an unperturbed 3D fold. Although reliant on genetic code expansion, StayRose provides an important step toward developing redshifted StayGold derivatives.

Journal of Biological Chemistry, December 2025

Cook Jonathan, Crow Allister

The FtsEX-EnvC-AmiA/B system is a key component of the E. coli cell division machinery that directs breakage of the peptidoglycan layer during separation of daughter cells. Structural and mechanistic studies have shown that ATP binding by FtsEX in the cytoplasm drives periplasmic conformational changes in EnvC, which lead to the binding and activation of peptidoglycan amidases such as AmiA and AmiB. The FtsEX-EnvC amidase system is highly regulated to prevent cell lysis with at least two separate layers of autoinhibition that must be relieved to initiate peptidoglycan hydrolysis during division. Here, we test the FtsEX-EnvC amidase activation mechanism through site-directed mutagenesis. We identify mutations that disrupt the autoinhibition mechanism of FtsEX-EnvC and an N-terminal deletion variant that prevents activation. Finally, we develop a cysteine locking residue pair that stabilizes the complex in its amidase activating conformation. The reported EnvC variants greatly enhance our understanding of the FtsEX-EnvC autoinhibition mechanism and the conformational changes underpinning amidase activation. Our observations are consistent with the proposed mechanism of amidase activation by large-scale conformational changes in FtsEX-EnvC, allowing recruitment and activation of peptidoglycan amidases.

MBIO-ASM Journals

Matt J. Keeling, Edward M. Hill, Stavros Petrou, Phuong Bich Tran, May Ee Png, Sophie Staniszewska, Corinna Clark, Katie Hassel, Julia Stowe, Nick Andrews

In England, and many other countries, immunity to SARS-CoV-2 infection and COVID-19 disease is highly heterogeneous.. During the height of the pandemic in England, the main aim was to rapidly protect the population and large supplies of vaccine were pre-purchased, eliminating the need for cost-effective calculations. As we move to an era where for the majority of the population SARS-CoV-2 infections cause relatively mild disease, and vaccine stocks need to be re-purchased, it is important we consider the cost-effectiveness and economic value of COVID-19 vaccination programmes. Here using data from 2023 and 2024 in England on COVID-19 hospital admissions, ICU admissions and deaths, coupled with bespoke health economic costs, we consider the willingness to pay threshold for COVID-19 vaccines in different age and risk groups.

Vaccine. March 2025

Michaël Dagne Tadesse, Nala Ali, Martha White, Lijiang Song, Fabrizio Alberti, Antonia P. Sagona 

There is an urgent need for novel antimicrobial therapies, chemical and nonantibiotic. The basidiomycota-derived, secondary metabolite pleurotin has been shown to be effective against Gram-positive bacteria, while bacteriophages could be the ultimate nonantibiotic alternative. In this study, the combination of pleurotin and phage K targeting S. aureus was examined. Pleurotin was isolated from the basidiomycota fungus Hohenbuehelia grisea. The cytotoxicity of pleurotin was assessed in two human cell lines in comparison to pleuromutilin, vancomycin, and phage K. The antibiotics were then tested independently or in combination with phage K against two S. aureus strains. Cytotoxicity of pleurotin in human cells was comparable to vancomycin and pleuromutilin. Results suggest that adding phage K has a synergistic effect and can lower the MIC for pleurotin, pleuromutilin, and vancomycin. This demonstrates that pleurotin could be a viable antistaphylococcal drug.

ACS Omega. March 2025

Matevz Papp-Rupar, Emily R. Grace, Naina Korotania, Maria-Laura Ciusa, Robert W. Jackson, Mojgan Rabiey

Isolation of phages targeting the cherry pathogen Pseudomonas syringae pv. syringae (Pss) led to five distinct phage genotypes. Building on previous in vitro coevolution experiments, the coevolution of the five phages (individually and as a cocktail) with Pss on cherry leaves was conducted in glasshouse and field experiments. Phages effectively reduced Pss numbers on detached leaves, with no evidence of phage resistance emerging in the bacterial population. Field application of phages in a cherry orchard in Southeast England evaluated phage survival, viability and impact on bacterial populations and the microbial community. The bacterial population and phages persisted in the leaf and shoot environment as long as the bacterial host was present. In contrast to in vitro studies, the plant environment constrained the emergence of phage resistant Pss populations.

Environmental Microbiology. March 2025

Niba Rawlings, Ngwa, Bailey, Mark and Courtenay, Orin

This systematic review and meta-analysis of data specific to military populations aims to identify knowledge gaps to mitigate sand fly exposure and Leishmania transmission during deployments. Regular use of long-lasting insecticidal nets to mitigate sand fly exposure demonstrated high potential effectiveness than other reported personal protective measures (PPMs) which yielded mixed or inconclusive results. In summary, the systematic review revealed the substantial variability between study designs and statistical integrity. There is need for more consistent and robustly designed studies including well-define controls and replication. Future studies would be advised to explore the long-term effectiveness and practicality of PPMs, both individually and in combination, across diverse deployment settings.

PLoS Neglected Tropical Diseases. March 2025

Glen Guyver-Fletcher, Erin E. Gorsich, Chris Jewell, Michael J. Tildesley

In this article we present a spatially-explicit stochastic metapopulation model to simulate the spread and control of foot-and-mouth disease (FMD) in an endemic setting. We parameterise and validate the model using detailed outbreak data from the Republic of Turkey, 2001–2012. Subsequently, we assess the efficacy of ring vaccination, mass vaccination, and livestock movement restrictions with regards to incidence-reduction and likelihood of eradication. Our results suggest countries wishing to control the disease within their borders should focus on comprehensive surveillance and vaccination campaigns as their main policy goals. In summary, vaccination-based policies are more effective than movement restrictions in the endemic context.

Infectious Disease Modelling.; February 2025

Zuyu Yang, Heather Davies, Jane Clapham, Liza Lopez, Holly B Bratcher, Audrey Tong, Xavier Didelot, Martin C.J. Maiden, Philip E. Carter, Xiaoyun Ren

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD), a form of bacterial meningitis and septicaemia, leading to isolated cases, outbreaks, and epidemics worldwide. Between 1991 and 2008, Aotearoa/New Zealand (NZ) experienced a prolonged hyperendemic group B IMD outbreak caused by the NZMenB epidemic strain. To understand NZMenB origin and initiation we used phylodynamic tools to analyse approximately 97 % of all NZMenB isolates submitted to the NZ Meningococcal Reference Laboratory from 1990 to 2019.. Our evidence from molecular dating and clonal expansion analysis suggests that NZMenB was circulating and had expanded before the epidemic. Comparison with international data showed multiple importations and re-introductions of NZMenB into NZ, while not suggesting close relationships with international variants. We propose the NZMenB epidemic may have been triggered by increasing societal inequality and household crowding resulting from government policies at the time.

Infection, Genetics and Evolution. February 2025

Alexander R Kaye, Giorgio Guzzetta, Michael J Tildesley

For many infectious diseases, the risk of outbreaks varies seasonally. If a pathogen is usually absent from a host population, a key public health policy question is whether the pathogen’s arrival will initiate local transmission, which depends on the season in which arrival occurs. This question can be addressed by estimating the “probability of a major outbreak” (the probability that introduced cases will initiate sustained local transmission). We have devised an approach for inferring outbreak risks for seasonal pathogens (involving calculating the Threshold Epidemic Risk; TER). Estimation of the TER involves calculating the probability that introduced cases will initiate a local outbreak in which a threshold number of cumulative infections is exceeded before outbreak extinction. For simple seasonal epidemic models, such as the stochastic Susceptible-Infectious-Removed model, the TER can be calculated numerically (without model simulations). For more complex models, such as stochastic host-vector models, the TER can be estimated using model simulations.

PLoS Computational Biology. February 2024

Sarbjit Nijjar, Deborah Brotherton, Jack Butler, Valentin-Mihai Dospinescu, Harry G Gannon, Victoria Linthwaite, Martin Cann, Alexander Cameron, Nicholas Dale 

CO2 directly modifies the gating of connexin26 (Cx26) gap junction channels and hemichannels. This gating depends upon Lys125, and the proposed mechanism involves carbamylation of Lys125 to allow formation of a salt bridge with Arg104 on the neighbouring subunit. We demonstrate via carbamate trapping and tandem mass spectrometry that five Lys residues within the cytoplasmic loop, including Lys125, are indeed carbamylated by CO2 . Our findings directly demonstrate carbamylation in connexins, provide further insight into the differential action of CO2 on Cx26 hemichannels and gap junction channels, and increase support for the role of the N-terminus in gating the Cx26 channel. KEY POINTS: Direct evidence of carbamylation of multiple lysine residues in the cytoplasmic loop of Cx26. Concentration-dependent carbamylation at lysines 108, 122 and 125. Only carbamylation of lysine 125 is essential for hemichannel opening to CO2. Carbamylation of lysine 108 along with lysine 125 is essential for CO2-dependent gap junction channel closure.

Journal of Physiology. February 2025

Julia A. Fairbairn, Rachel V. Kerr, Nika-Kare A. Pierre-White, Anthony Jacovides, Becca W. A. Baileeves, Phillip J. Stansfeld, Gerhard Bringmann, Andrew T. Merritt and Timothy D. H. Bugg

Escherichia coli translocase MraY is the target for bacteriolytic protein E from bacteriophage fX174, interacting at a site close to Phe-288 on helix 9, on the extracellular face of the protein. A peptide motif Arg-Trp-x-x-Trp from protein E was used to design a set of triazinedione peptidomimetics, which inhibit particulate MraY (6d IC50 48 µM), and show antimicrobial activity against Gram-negative and Gram-positive antibiotic-resistant clinical strains (7j MIC Acinetobacter baumannii 16 µg/mL, Staphyloccoccus aureus MRSA 2-4 µg/mL). Docking against a predicted structure for E. coli MraY revealed two possible binding sites close to helix 9, the binding site for protein E. Antimicrobial activity of analogue 6j was found to be synergistic with bacitracin in Micrococcus flavus, consistent with a link between this inhibition site and undecaprenyl phosphate uptake. Alkaloid michellamine B, also predicted to bind in the cleft adjacent to helix 9, was also found to be synergistic with bacitracin. These data provide experimental evidence that the unusual hydrophobic cleft adjacent to helix 9 in MraY is involved in uptake of undecaprenyl phosphate, in addition to recently identified transporters UptA and PopT, and that this process can be targetted by small molecules as a novel antibacterial mechanism.

RSC Medicinal Chemistry. January 2025

Helekal, David, Koskela, Jere and Didelot, Xavier

Here we consider the problem of detecting the presence of multiple mergers in the context of dating a phylogeny, that is determining the date of each of the nodes. We use the Lambda-coalescent theory as a modelling framework and show how Bayesian inference can be efficiently performed using a Billera-Holmes- Vogtmann space embedding and a customised Markov Chain Monte Carlo sampling scheme. We applied this new analysis methodology to a large number of simulated datasets to show that it is possible to infer if and when multiple merger events occurred, and that the phylogenetic dating is improved as a result of taking this information into account. We also analysed real datasets of Vibrio cholerae and Mycobacterium tuberculosis to demonstrate the relevance of our approach to real pathogen evolutionary epidemiology. We have implemented our new methodology in a R package which is freely available at https://github.com/dhelekal/MMCTime.

Systematic Biology. January 2025

Zdouc, Mitja M. et al inc. Alberti, F

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard.

Nucleic Acids Research. January 2025

Kelsey Cremin, Gabriel N. Meloni, Orkun S. Soyer, Patrick R. Unwin

This work presents an experimental platform combining scanning ion conductance microscopy (SICM) with confocal laser scanning microscopy (CLSM), using intra- and extracellular pH indicator dyes to study the impact of acid delivery on individual HeLa cells within a population.. We find a strong dependency between the intracellular pH and the extracellular pH gradient imposed by local acid delivery. Postdelivery intracellular pH recovery depends on the extent of the acid challenge, with cells exposed to lower pH not returning to basal intracellular pH values after the extracellular pH recovers. This is a unique method for concentration-gradient challenge studies of cell populations that will have broad applications in cell biology. SICM can be used to deliver different chemicals and enables a wide range of local conditions to be applied across a cell population, for which the effects can be investigated at the single-cell level.

ACS Measurement Science. January 2025

Pawel K Lysyganicz, Antonio D Barbosa, Shoily Khondker, Nicolas A Stewart, George M Carman, Phillip J Stansfeld, Marcus K Dymond, Symeon Siniossoglou

Here we demonstrate that a lipid-degradation pathway inhibits expansion of the endoplasmic reticulum (ER) membrane. Phospholipid diacylglycerol acyltransferases (PDATs) use endogenous phospholipids as fatty-acyl donors to generate triglyceride stored in lipid droplets. The significance of this non-canonical triglyceride biosynthesis pathway has remained elusive. We show that active Lro1 mediates retraction of ER membrane expansion driven by phospholipid synthesis. Furthermore, subcellular distribution and membrane turnover activity of Lro1 are controlled by diacylglycerol produced by the activity of Pah1, a conserved member of the lipin family. Collectively, our findings reveal a lipid-metabolic network that regulates endoplasmic reticulum biogenesis by converting phospholipids into storage lipids.

EMBO Journal. January 2025

Structure of the Nipah virus polymerase complex

Esra Balıkçı, Franziska Günl, Loïc Carrique, Jeremy R Keown, Ervin Fodor, Jonathan M Grimes

Nipah virus is a highly virulent zoonotic paramyxovirus causing severe respiratory and neurological disease. Despite its lethality, there is no approved treatment for Nipah virus infection. The viral polymerase complex, composed of the polymerase (L) and phos-phoprotein (P), replicates and transcribes the viral RNA genome. Here, we describe structures of the Nipah virus L-P polymerase complex and the L-protein’s Connecting Domain (CD). Our findings offer insights into the structural details of the L-P polymerase complex and the molecular interactions between L-proteinand P-protein, shedding light on the mechanisms of the replicationmachinery. This work will underpin efforts to develop antiviraldrugs that target the polymerase complex of Nipah virus.

EMBO Journal. December 2024.

Structural characterization of the full-length Hantaan virus polymerase

Hantaviridae are a family of segmented negative-sense RNA viruses that contain important human and animal pathogens. Hantaviridae contain a viral RNA-dependent RNA polymerase that replicates and transcribes the viral genome. Here we establish the expression and purification of the polymerase from the Old World Hantaan virus and characterise the structure using Cryo-EM. The insights gained here guide future mechanistic studies of both the transcription and replication activities of the hantavirus polymerase and for the development of therapeutic targets.

PLoS Pathogens. December 2024

Felipe J Medina-Aguayo, Xavier Didelot, Richard G Everitt

Bacteria reproduce clonally but most species recombine frequently, so that the ancestral process is best captured using an ancestral recombination graph. This graph model is often too complex to be used in an inferential setup, but it can be approximated for example by the ClonalOrigin model. Inference in the ClonalOrigin model is performed via a Reversible-Jump Markov Chain Monte Carlo algorithm, however this often performs poorly due to the complexity of the target distribution since it needs to explore spaces of different dimensions. Recent developments in Bayesian computation methodology have provided ways to improve existing methods and code, but are not well-known outside the statistics community. We show how exploiting one of these new computational methods can lead to faster inference under the ClonalOrigin model.

Bayesian Analysis. December 2024

Diana Vinchira-Villarraga, Sabrine Dhaouadi, Vanja Milenkovic, Jiaqi Wei, Emily R. Grace, Katherine G. Hinton, Amy J. Webster, Andrea Vadillo-Dieguez, Sophie E. Powell, Naina Korotania, Leonardo Castellanos, Freddy A. Ramos, Richard J. Harrison, Mojgan Rabiey & Robert W. Jackson

This study aimed to develop a methodological approach to obtain extracts from different tree species with the highest reproducibility and chemical diversity possible, to ensure proper coverage of the trees’ metabolome. Each tree species has a unique metabolic profile, which means that no single protocol is universally effective. Extraction at 50 °C for three cycles using 80% methanol or chloroform/methanol/water showed the best results and is suggested for studying wood metabolome. These observations highlight the need to tailor extraction protocols to each tree species to ensure comprehensive metabolome coverage for metabolic profiling.

Metabolomics. December 2024

Valeriya Bezkorovayna, Brooke K. Hayes, Francesca N. Gillett, Amy Wright, David I. Roper, Marina Harper, Sheena McGowan, John D. Boyce

Acinetobacter baumannii is a Gram-negative opportunistic pathogen and is a common cause of nosocomial infections.). Here we define the regions of interaction between Tae17 and its cognate delivery protein VgrG17 and identify that amino acids G1069 and W1075 in VgrG17 are essential for Tae17 delivery via the T6SS, the first time such specific delivery determinants of T6SS cargo effectors have been defined. Furthermore, we determine that the Tae17 effector is a multidomain, bifunctional, peptidoglycan-degrading enzyme that has both amidase activity, which targets the sugar-peptide bonds, and lytic transglycosylase activity, which targets the peptidoglycan sugar backbone. Moreover, we show that the Tae17 transglycosylase activity is more important than amidase activity for the killing of Escherichia coli. This study provides molecular insight into how the T6SS allows A. baumannii strains to gain dominance in polymicrobial communities and thus improve their chances of survival and transmission.

mBio. December 2024

The impact of natural climate variability on the global distribution of Aedes aegypti : a mathematical modelling study

Kaye, A. R., Obolski, U., Sun, L., Hart, W. S., Hurrell, J. W., Tildesley, M. J. and Thompson, R. N.

Aedes aegypti spread pathogens affecting humans, including dengue, Zika, and yellow fever viruses. Anthropogenic climate change is altering the spatial distribution of Ae aegypti and therefore the locations at risk of vector-borne disease. In addition to climate change, natural climate variability, resulting from internal atmospheric processes and interactions between climate system components (eg, atmosphere–land and atmosphere–ocean interactions), determines climate outcomes. However, the role of natural climate variability in modifying the effects of anthropogenic climate change on future environmental suitability for Ae aegypti has not been assessed fully. In this study, we aim to assess uncertainty arising from natural climate variability in projections of Ae aegypti suitability up to the year 2100. Lancet Planetary Health. December 2024

The time between symptom onset and various clinical outcomes : a statistical analysis of MERS-CoV patients in Saudi Arabia

Althobaity, Yehya, Alkhudaydi, Muhammad, Hill, Edward M., Thompson, Robin N. and Tildesley, Michael J

In this study, we investigate the impact of demographic characteristics on MERS-CoV cases in Saudi Arabia, specifically focusing on the time intervals between symptom onset and key events such as hospitalization, case confirmation, reporting and death. Importantly, we observe age-based differences in the risk of hospitalization and other measures of infection severity, including the probability of death conditional on hospitalization. Careful quantification of epidemiological characteristics, including inference of key epidemiological periods and assessments of differences between cases of different ages, plays a crucial role in understanding the progression of MERS-CoV outbreaks and formulating effective public health strategies to mitigate their impact.

Royal Society Open Society. November 2024

Kołodziej, Marta, Tsapras, Panagiotis, Cameron, Alexander and Nezis, Ioannis P

LC3 (microtubule-associated protein 1 light chain 3, called Atg8 in yeast and Drosophila) is one of the most well-studied autophagy-related proteins. LC3 controls the selectivity of autophagic degradation by interacting with LIR (LC3-interacting region) motifs also known as AIM (Atg8-interacting motifs) on selective autophagy receptors that carry cargo for degradation. Although the function of Atg8 family proteins is primarily cytoplasmic, they are also enriched in the nucleus. Here, we used yeast two-hybrid screening, and we identified transcription factor Deformed wings (Dwg) as an Atg8a-interacting protein in Drosophila. Dwg-Atg8a interaction is LIR motif-dependent. We have created Dwg Y129A/I132A LIR mutant flies and shown that they exhibit elevated autophagy, improved resistance to oxidative stress, and starvation. Our results provide novel insights into the transcriptional regulation of autophagy in Drosophila.

Cells. November 2024

Claudia Simm, Tzong-Hsien Lee, Harshini Weerasinghe, Dean Walsh, Ioanna T Nakou, Madhu Shankar, Wai Chung Tse, Rebecca Inman, Robert J Mulder, Freya Harrison, Marie-Isabel Aguilar, Gregory L Challis, Ana Traven

Amphotericin B (AmpB) is an effective but toxic antifungal drug.. AmpB disrupts fungal membranes by two proposed mechanisms: ergosterol sequestration from the membrane and pore formation. Whether these two mechanisms operate in conjunction and how they could be potentiated remains to be fully understood. Here, we report that gladiolin, a polyketide antibiotic produced by Burkholderia gladioli, is a strong potentiator of AmpB and acts synergistically against Cryptococcus and Candida species, including drug-resistant C. auris. Gladiolin also synergizes with AmpB against drug-resistant fungal biofilms, while exerting no mammalian cytotoxicity.. Collectively, our findings shed light on AmpB’s mechanism of action and characterize gladiolin as an AmpB potentiator, showing an antifungal mechanism distinct from its proposed antibiotic activity. We shed light on the synergistic mechanism at the membrane, and provide insights into potentiation strategies to improve AmpB’s activity/toxicity relationship.

mBio. November 2024

Chris L B Graham, Jack Bryant, David I Roper, Manuel Banzhaf 

Here we describe a method for in vivo phospholipid labelling by fluorescent imaging in Pseudomonas aeruginosa using a phosphatidylcholine (PC) mimic, “propargyl-choline”(PCho). This click-chemistry liable headgroup mimic is visible by microscopy and allows the covalent labelling of lipids. Fluorescence of the cell membranes, visible in heterogenous patches, is dependent on PCho concentration and is localised in the membrane fraction of cells, demonstrating that it is suitable for membrane labelling and cell imaging.

Access Microbiology. November 2024

Nathan J. Burton, Luís D R. Melo, Michaël F D. Tadesse, Bethany Pearce, Evangelos Vryonis, Antonia P. Sagona

In this study, we produced a cocktail of novel bacteriophages and assessed their viability to eradicate nosocomial staphylococcal biofilms. Here, we used clinical isolates from prosthetic joint infections to isolate and identify four new bacteriophages from sewage effluent. These novel phages were characterized through electron microscopy and full genome sequencing. Subsequently, we combined them into a phage cocktail, which effectively re-sensitized biofilms to vancomycin and flucloxacillin. Notably, this phage cocktail demonstrated low cytotoxicity in vitro to human epithelial cells, even when used alongside antibiotic treatments. These findings highlight the potential of the phage cocktail as a tool to increase antibiotic treatment success in prosthetic joint infections.

Sustainable Microbiology. November 2024