A5055049959- Antibiotic Resistance in Bacteria
- Genomics and Phylogenetic Studies
- Mycobacterium research and diagnosis
- Bacterial Identification and Susceptibility Testing
- Gut microbiota and health
- Molecular Biology Techniques and Applications
- Evolution and Genetic Dynamics
- Cancer Genomics and Diagnostics
- Yersinia bacterium, plague, ectoparasites research
- Pharmaceutical and Antibiotic Environmental Impacts
- Oral microbiology and periodontitis research
- Zoonotic diseases and public health
- Bacteriophages and microbial interactions
- Animal Disease Management and Epidemiology
- Antibiotics Pharmacokinetics and Efficacy
- Tuberculosis Research and Epidemiology
- Antibiotic Use and Resistance
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Microbial infections and disease research
- Plant Pathogenic Bacteria Studies
- Innovations in Concrete and Construction Materials
- Plant Virus Research Studies
- Enterobacteriaceae and Cronobacter Research
- RNA and protein synthesis mechanisms
University of Oxford
2015-2024
Durham University
2022-2024
John Radcliffe Hospital
2018-2023
University College London
2016-2021
ORCID
2021
Nuffield Health
2020
University of Leeds
2019
University of Amsterdam
2019
Institute of Infection and Immunity
2018
Abstract Large structural variations (SVs) within genomes are more challenging to identify than smaller genetic variants but may substantially contribute phenotypic diversity and evolution. We analyse the effects of SVs on gene expression, quantitative traits intrinsic reproductive isolation in yeast Schizosaccharomyces pombe . establish a high-quality curated catalogue worldwide library S. strains, including duplications, deletions, inversions translocations. show that copy number (CNVs)...
Abstract Colistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae . As such, recent plasmid-mediated spread colistin resistance gene mcr-1 poses a significant public health threat, requiring global monitoring and surveillance. Here, we characterize distribution using data set 457 mcr-1- positive sequenced isolates. We find in various plasmid types but identify an immediate background common to all sequences. Our analyses...
Abstract COVID-19 is caused by the coronavirus SARS-CoV-2, which jumped into human population in late 2019 from a currently uncharacterised animal reservoir. Due to this recent association with humans, SARS-CoV-2 may not yet be fully adapted its host. This has led speculations that evolving towards higher transmissibility. The most plausible mutations under putative natural selection are those have emerged repeatedly and independently (homoplasies). Here, we formally test whether any...
Illumina sequencing allows rapid, cheap and accurate whole genome bacterial analyses, but short reads (<300 bp) do not usually enable complete assembly. Long-read greatly assists with resolving complex genomes, particularly when combined short-read data (hybrid assembly). However, it is clear how different long-read methods affect hybrid assembly accuracy. Relative automation of the process also crucial to facilitating high-throughput reconstruction, avoiding multiple bespoke filtering...
Abstract The mobile resistance gene bla NDM encodes the enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some most severe bacterial infections. is globally distributed across variety Gram-negative bacteria on multiple plasmids, typically located within highly recombining and transposon-rich genomic regions, leads dynamics underlying global dissemination remain poorly resolved. Here, we compile dataset over 6000 genomes harbouring gene, including 104 newly generated...
Treatment with antibiotics is one of the most extreme perturbations to human microbiome. Even standard courses dramatically reduce microbiome's diversity and can cause transitions dysbiotic states. Conceptually, this often described as a 'stability landscape': microbiome sits in landscape multiple stable equilibria, sufficiently strong shift from its normal equilibrium another state. However, picture only qualitative has not been incorporated previous mathematical models effects antibiotics....
Abstract Background Accurately identifying single-nucleotide polymorphisms (SNPs) from bacterial sequencing data is an essential requirement for using genomics to track transmission and predict important phenotypes such as antimicrobial resistance. However, most previous performance evaluations of SNP calling have been restricted eukaryotic (human) data. Additionally, requires choosing appropriate reference genome align reads to, which, together with the bioinformatic pipeline, affects...
The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed salivary microbiomes of an extended family Ashkenazi Jewish individuals living in several cities investigated associations with both shared household genetic similarities. We found that environmental effects dominated over effects. While there was weak evidence geographical structuring at level cities, observed a large significant effect on composition, supporting...
Abstract Maladaptation to modern diets has been implicated in several chronic disorders. Given the higher prevalence of disease such as dental caries and gum diseases industrialized societies, we sought investigate impact different subsistence strategies on oral health physiology, documented by microbiome. To control for confounding variables environment host genetics, sampled saliva from three pairs populations hunter‐gatherers traditional farmers living close proximity Philippines. Deep...
Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as ‘one-stop’ test epidemiological predictive AST results. Few published comparisons exist myriad analytical pipelines used predicting AMR. To address this, we performed an inter-laboratory study providing sets of...
Many major human pathogens are multihost pathogens, able to infect other vertebrate species. Describing the general patterns of host-pathogen associations across pathogen taxa is therefore important understand risk factors for disease emergence. However, there a lack comprehensive curated databases this purpose, with most previous efforts focusing on viruses. Here, we report largest manually compiled association database, covering 2,595 bacteria and viruses infecting 2,656 hosts. We also...
Abstract Background Shotgun metagenomics is increasingly used to characterise microbial communities, particularly for the investigation of antimicrobial resistance (AMR) in different animal and environmental contexts. There are many approaches inferring taxonomic composition AMR gene content complex community samples from shotgun metagenomic data, but there has been little work establishing optimum sequencing depth, data processing analysis methods these samples. In this study we cultured...
Abstract The COVID-19 pandemic is caused by the coronavirus SARS-CoV-2, which jumped into human population in late 2019 from a currently uncharacterised animal reservoir. Due to this extremely recent association with humans, SARS-CoV-2 may not yet be fully adapted its host. This has led speculations that some lineages of evolving towards higher transmissibility. most plausible candidate mutations under putative natural selection are those have emerged repeatedly and independently...
The pangenome of Escherichia coli from nearby farms shows how livestock host and local geography shape bacterial populations.
Repeated culture reduces within-sample Mycobacterium tuberculosis genetic diversity due to selection of clones suited growth in and/or random loss lineages, but it is not known what extent omitting the step altogether alters diversity. We compared M. whole genome sequences generated from 33 paired clinical samples using two methods. In one method DNA was extracted directly sputum then enriched with custom-designed SureSelect (Agilent) oligonucleotide baits and other mycobacterial indicator...
Many novel traits such as antibiotic resistance are spread by plasmids between species. Yet have different host ranges. Restriction-modification systems (R-M systems) far the most abundant bacterial defense system and therefore represent one of key barriers to plasmid spread. However, their effect on evolution range has been neglected. Here we analyse avoidance targets R-M (Type II) for complete genomes across diversity. For common target length (6 bp) show that is strongly correlated with...
Abstract Antibiotic resistance poses a global health threat, but the within-host drivers of remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and is thought emerge due selection for de novo variants. Here we show that mixed strain common in opportunistic pathogen P. aeruginosa . Crucially, evolves rapidly patients colonized by multiple strains through pre-existing resistant strains. In contrast, sporadically single novel mutations. However, strong...
ABSTRACT Illumina sequencing allows rapid, cheap and accurate whole genome bacterial analyses, but short reads (<300 bp) do not usually enable complete assembly. Long read greatly assists with resolving complex genomes, particularly when combined short-read data (hybrid assembly). However, it is clear how different long-read methods impact on assembly accuracy. Relative automation of the process also crucial to facilitating high-throughput reconstruction, avoiding multiple bespoke...
The genomic diversity of microbes is commonly parameterized as SNPs relative to a reference genome well-characterized, but arbitrary, isolate. However, any contains only fraction the microbial pangenome , total set genes observed in given species. Reference-based approaches are thus blind dynamics accessory genome, well variation within gene order and copy number. With widespread usage long-read sequencing, number high-quality, complete assemblies has increased dramatically. In addition...
The effect of secondary structure on DNA duplex formation is poorly understood. Using oxDNA, a nucleotide level coarse-grained model DNA, we study how hairpins influence the rate and reaction pathways hybridzation. We compare to experimental systems studied by Gao et al. (1) find that 3-base pair reduce hybridization factor 2, 4-base 10, compared with limited structure, which in good agreement experiments. By contrast, melting rates are accelerated factors ∼100 ∼2000. This surprisingly large...
Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing healthcare-associated (HA-MRSA) ST239. We showed that isolates tend to competitive advantage growth experiments against However,...
Enterobacterales from livestock are potentially important reservoirs for antimicrobial resistance (AMR) to pass through the food chain humans, thereby increasing AMR burden and affecting our ability tackle infections. In this study 168 isolates four genera of order , primarily Escherichia coli were purified (cattle, pigs sheep) faeces 14 farms in United Kingdom. Their genomes resolved using long- short-read sequencing analyse genes their genetic context, as well explore relationship between...