Latest Publications
Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis
Camus Nimmo, Arturo Torres Ortiz, Cedric C. S. Tan, Juanita Pang, Mislav Acman, James Millard, Nesri Padayatchi, Alison D. Grant, Max O’Donnell, Alex Pym, Ola B. Brynildsrud, Vegard Eldholm, Louis Grandjean, Xavier Didelot, François Balloux & Lucy van Dorp
Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug. We compiled a dataset of 3682 Mtb genomes, including 180 carrying variants in mmpR5, and its immediate background (i.e. mmpR5 promoter and adjacent mmpL5 gene), that have been associated to borderline (henceforth intermediate) or confirmed resistance to bedaquiline. We characterised the occurrence of all nonsynonymous mutations in mmpR5 in this dataset and estimated, using time-resolved phylogenetic methods, the age of their emergence.
The long and short of it: benchmarking viromics using Illumina, Nanopore and PacBio sequencing technologies
Ryan Cook, Nathan Brown, Branko Rihtman, Slawomir Michniewski, Tamsin Redgwell, Martha Clokie, Dov J. Stekel, Yin Chen, David J. Scanlan, Jon L. Hobman, Andrew Nelson, Michael A. Jones, Darren Smith and Andrew Millard
ecology. Long-read sequencing and hybrid assembly approaches that combine long- and short-read technologies are now being widely implemented in bacterial genomics and metagenomics. However, the use of long-read sequencing to investigate viral communities is still in its infancy. While Nanopore and PacBio technologies have been applied to viral metagenomics, it is not known to what extent different technologies will impact the reconstruction of the viral community. Thus, we constructed a mock bacteriophage community of previously sequenced phage genomes and sequenced them using Illumina, Nanopore and PacBio sequencing technologies and tested a number of different assembly approaches. Overall the best approach was assembly by a combination of Illumina and Nanopore reads, which reduced error rates to levels comparable with short-read-only assemblies. When using a single technology, Illumina only was the best approach. These findings will provide a starting point for others in the choice of reads and assembly algorithms for the analysis of viromes.
Liver sinusoidal cells eliminate blood-borne phage K1F
Javier Sánchez Romano, Jaione Simón-Santamaria, Peter McCourt, Bård Smedsrød, Kim Erlend Mortensen, Antonia P. Sagona, Karen Kristine Sørensen, Anett Kristin Larsen
Blood-borne phages are believed to be captured by macrophages in the liver and spleen. Since liver sinusoids also consist of specialized scavenger liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), this study investigated the contribution of both cell types in the elimination of Escherichia coli phage K1Fg10b::gfp (K1Fgfp) in mice. The results presented herein contribute to increased knowledge about the pharmacokinetics of the T7-like phage K1F in the mammalian system. The cell types of the liver that are responsible for rapid phage blood clearance are identified. Our results highlight the need for more research about appropriate dose regimens when phage therapy is delivered intravenously and advise essential knowledge about cell systems that should be investigated further for detailed phage pharmacodynamics.
First archaeological evidence for ginger consumption as a potential medicinal ingredient in a late medieval leprosarium at St Leonard, Peterborough, England
Elena Fiorin, Charlotte A. Roberts, Marica Baldoni, Erin Connelly, Christina Lee, Claudio Ottoni & Emanuela Cristiani
Leprosy was one of the most outwardly visible diseases in the European Middle Ages, a period during which leprosaria were founded to provide space for the sick. In the present study, microremains and DNA were analysed from the calculus of individuals buried in the late medieval cemetery of St Leonard, a leprosarium located in Peterborough, England. The results show the presence of ginger (Zingiber officinale), a culinary and medicinal ingredient, as well as evidence of consumption of cereals and legumes. This research suggests that affected individuals consumed ingredients mentioned in medieval medical textbooks that were used to treat regions of the body typically impacted by leprosy. To the authors' knowledge, this is the first study which has identified Zingiber officinale in human dental calculus in England or on the wider European continent.
Xavier Didelot publications
Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes
Y Wan, AC Myall, A Boonyasiri, F Bolt, A Ledda, S Mookerjee, AY Weiße, M Getino, JF Turton, H Abbas, R Prakapaite, A Sabnis, A Abdolrasouli, K Malpartida-Cardenas, L Miglietta, H Donaldson, M Gilchrist, KL Hopkins, MJ Ellington, JA Otter, G Larrouy-Maumus, M Edwards, J Rodriguez-Manzano, X Didelot, M Barahona, AH Holmes, E Jauneikaite, F Davies
Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. Our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.
Journal of Infectious Diseases. January 2024
Genomic epidemiology of the clinically dominant clonal complex 1 in the Listeria monocytogenes population in the UK
Emily T. Fotopoulou, Claire Jenkins, Clare R. Barker, Anais Painset, Xavier Didelot, Ameze Simbo, Amy Douglas, Gauri Godbole, Frieda Jorgensen, Saheer Gharbia, Jim McLauchlin
Listeria monocytogenes is a food-borne pathogen, typically affecting the elderly, immunocompromised patients and pregnant women. The aim of this study was to determine the population structure of L. monocytogenes clonal complex 1 (CC1) in the UK and describe the genomic epidemiology of this clinically significant CC. We interrogated a working dataset of 4073 sequences of L. monocytogenes isolated between January 2015 and December 2020 from human clinical specimens, food and/or foodproduction environments. Analysis of demographic and clinical outcome data identified CC1 as a clinically significant cause of invasive listeriosis in the elderly population and in women of child-bearing age. Phylogenetic analysis revealed the population structure of CC1 in the UK comprised small, sparsely populated genomic clusters. Only clusters containing isolates from an implicated food vehicle, or food processing or farming environments, were resolved, emphasizing the need for clinical, food and animal-health agencies to share sequencing data in real time, and the importance of a One Health approach to public-health surveillance of listeriosis.
Temporal changes in the positivity rate of common enteric viruses among paediatric admissions in coastal Kenya, during the COVID-19 pandemic, 2019-2022
Arnold W. Lambisia, Nickson Murunga, Martin Mutunga, Robinson Cheruiyot, Grace Maina, Timothy O. Makori, D. James Nokes and Charles N. Agoti
The non-pharmaceutical interventions (NPIs) implemented to curb the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic, substantially disrupted the activity of other respiratory viruses. However, there is limited data from low-and-middle income countries (LMICs) to determine whether these NPIs also impacted the transmission of common enteric viruses. Here, we investigated the changes in the positivity rate of five enteric viruses among hospitalised children who presented with diarrhoea to a referral hospital in coastal Kenya, during COVID-19 pandemic period. Our study finds that in 2020 the transmission of common enteric viruses, especially RVA and astrovirus, in Kilifi Kenya may have been disrupted due to the COVID-19 NPIs. After 2020, local enteric virus transmission patterns appeared to return to pre-pandemic levels coinciding with the removal of most of the government COVID-19 NPIs.