Latest Publications
Mitochondrial and microbial diversity of the invasive mosquito vector species Culex tritaeniorhynchus across its extensive inter-continental geographic range
Claire L. Jeffries, Luciano M Tantely, Perparim Kadriaj, Marcus S C Blagrove, Ioanna Lytra, James Orsborne, Hasan Mohammad Al-Amin, Abdul Rahim Mohammed, Mohammad Shafiul Alam, Romain Girod, Yaw A Afrane, Silvia Bino, Vincent Robert, Sebastien Boyer, Matthew Baylis, Enkelejda Velo, Grant L Hughes, Thomas Walker
In this study, we used laboratory vector competence experiments to determine if Cx. tritaeniorhynchus from a Southern European population were competent JEV vectors. We obtained samples from multiple geographically dispersed Cx. tritaeniorhynchus populations from countries within Europe, Africa, Eurasia and Asia to perform phylogenetic analysis to measure the level of mitochondrial divergence using the cytochrome oxidase subunit 1 (CO1) gene. We also undertook bacterial 16S rRNA gene amplicon sequencing to determine microbial diversity and used multi-locus sequence typing (MLST) to determine any evidence for the presence of strains of the naturally occurring endosymbiotic bacterium Wolbachia. Cx. tritaeniorhynchus from a Greek population were shown be be competent vectors of JEV with high levels of virus present in saliva. We found a signficant level of mitochondrial genetic diversity using the mosquito CO1 gene between geographically dispersed populations. Furthermore, we report diverse microbiomes identified by 16S rRNA gene amplicon sequencing within and between geographical populations. Evidence for the detection of the endosymbiotic bacteria Wolbachia was confirmed using Wolbachia-specific PCR and MLST.
Response patterns of the microbiome during hexavalent chromium remediation by Tagetes erecta L
Juanjuan Xiao, Deying Wang, Banerjee Sinchan, Ryan Mushinski, Decai Jin, Ye Deng
Chromium pollution, particularly hexavalent chromium [Cr(VI)], may threaten the environment and human health. This study investigated the potential of Tagetes erecta L. (Aztec marigold) for phytoremediation of soil contaminated with Cr(VI), and focused on the effects of varying concentrations of Cr(VI) on both the physicochemical properties of soil and microbiome of Tagetes erecta L. We observed that Tagetes erecta L. showed tolerance to Cr(VI) stress and maintained normal growth under these conditions, as indicated by bioconcentration factors of 0.33–0.53 in shoots and 0.39–0.70 in roots. Meanwhile, the structure and diversity of bacterial communities were significantly affected by Cr(VI) pollution. This study explored the interactions between heavy metals, microorganisms, and plants, providing valuable insights for developing in situ bioremediation of Cr(VI)-contaminated soils.
Membraneless channels sieve cations in ammonia-oxidizing marine archaea
Andriko von Kügelgen, C. Keith Cassidy, Sofie van Dorst, Lennart L. Pagani, Christopher Batters, Zephyr Ford, Jan Löwe, Vikram Alva, Phillip J. Stansfeld & Tanmay A. M. Bharat
Nitrosopumilus maritimus is an ammonia-oxidizing archaeon that is crucial to the global nitrogen cycle. A critical step for nitrogen oxidation is the entrapment of ammonium ions from a dilute marine environment at the cell surface and their subsequent channelling to the cell membrane of N. maritimus. Here we elucidate the structure of the molecular machinery responsible for this process, comprising the surface layer (S-layer), using electron cryotomography and subtomogram averaging from cells. We supplemented our in situ structure of the ammonium-binding S-layer array with a single-particle electron cryomicroscopy structure, revealing detailed features of this immunoglobulin-rich and glycan-decorated S-layer. This in situ structural study illuminates the biogeochemically essential process of ammonium binding and channelling, common to many marine microorganisms that are fundamental to the nitrogen cycle.
Xavier Didelot publications
Presence of phage-plasmids in multiple serovars of Salmonella enterica
Satheesh Nair, Clare R. Barker, Matthew Bird, David R. Greig, Caitlin Collins, Anaïs PainsetMarie Chattaway, Derek Pickard, Lesley Larkin, Saheer Gharbia, Xavier Didelot and Paolo Ribeca
Evidence is accumulating in the literature that the horizontal spread of antimicrobial resistance (AMR) genes mediated by bacteriophages and bacteriophage-like plasmid (phage-plasmid) elements is much more common than previously envisioned. For instance, we recently identified and characterized a circular P1-like phage-plasmid harbouring a blaCTX-M-15 gene conferring extended-spectrum beta-lactamase (ESBL) resistance in Salmonella enterica serovar Typhi. As the prevalence and epidemiological relevance of such mechanisms has never been systematically assessed in Enterobacterales, in this study we carried out a follow-up retrospective analysis of UK Salmonella isolates previously sequenced as part of routine surveillance protocols between 2016 and 2021. In addition to providing a first comprehensive view of the presence of phage-plasmids in Salmonella, our work highlights the need for a better surveillance and understanding of phage-plasmids as AMR carriers, especially through their characterization with long-read sequencing. Microbial Genomics. May 2024
Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes
The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks. Nature Communications. May 2024
Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?
Vasconcelos, Andreia, King, Jonathan D., Nunes-Alves, Cláudio, Anderson, Roy, Argaw, Daniel, Basáñez, Maria-Gloria, Bilal, Shakir, Blok, David J., Blumberg, Seth, Borlase, Anna, Brady, Oliver J., Browning, Raiha, Chitnis, Nakul, Coffeng, Luc E., Crowley, Emily H, Cucunubá, Zulma M., Cummings, Derek A. T., Davis, Christopher N., Davis, Emma L., Dixon, Matthew, Dobson, Andrew, Dyson, Louise et al
Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021–2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.
Jeremy Keown publications
Structural and functional characterization of the interaction between the influenza A virus RNA polymerase and the CTD of host RNA polymerase II
Keown, Jeremy, Baazaoui, Alaa, Šebesta, Marek, Štefl, Richard, Carrique, Loïc, Fodor, Ervin, Grimes, Jonathan M.
Influenza A viruses, causing seasonal epidemics and occasional pandemics, rely on interactions with host proteins for their RNA genome transcription and replication. The viral RNA polymerase utilizes host RNA polymerase II (Pol II) and interacts with the serine 5 phosphorylated (pS5) C-terminal domain (CTD) of Pol II to initiate transcription. Our study, using single-particle electron cryomicroscopy (cryo-EM), reveals the structure of the 1918 pandemic influenza A virus polymerase bound to a synthetic pS5 CTD peptide composed of four heptad repeats mimicking the 52 heptad repeat mammalian Pol II CTD.. Our findings not only deepen our understanding of the influenza virus life cycle but also pinpoint a potential target for antiviral development. By elucidating the structural and functional aspects of the influenza virus polymerase-host Pol II interaction, this research provides a foundation for designing interventions to disrupt viral replication and transcription, offering promising avenues for future antiviral therapies.
Structures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation
Replication of avian IAVs in mammalian cells is hindered by species-specific variation in acidic nuclear phosphoprotein 32 (ANP32) proteins, which are essential for viral RNA genome replication. Adaptive mutations enable the IAV RNA polymerase (FluPolA) to surmount this barrier. Here, we present cryo-electron microscopy structures of monomeric and dimeric avian H5N1 FluPolA with human ANP32B. ANP32B interacts with the PA subunit of FluPolA in the monomeric form, at the site used for its docking onto the C-terminal domain of host RNA polymerase II during viral transcription. ANP32B acts as a chaperone, guiding FluPolA towards a ribonucleoprotein-associated FluPolA to form an asymmetric dimer—the replication platform for the viral genome. These findings offer insights into the molecular mechanisms governing IAV genome replication, while enhancing our understanding of the molecular processes underpinning mammalian adaptations in avian-origin FluPolA. Nature Communications. May 2024