Edward J Feil

Swansea University, Swansea, Wales, United Kingdom

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Publications (115)817.76 Total impact

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    ABSTRACT: Rapidly assaying the diversity of a bacterial species present in a sample obtained from a hospital patient or an evironmental source has become possible after recent technological advances in DNA sequencing. For several applications it is important to accurately identify the presence and estimate relative abundances of the target organisms from short sequence reads obtained from a sample. This task is particularly challenging when the set of interest includes very closely related organisms, such as different strains of pathogenic bacteria, which can vary considerably in terms of virulence, resistance and spread. Using advanced Bayesian statistical modelling and computation techniques we introduce a novel method for bacterial identification that is shown to outperform the currently leading pipeline for this purpose. Our approach enables fast and accurate sequence based identification of bacterial strains while using only modest computational resources. Hence it provides a useful tool for a wide spectrum of applications, including rapid clinical diagnostics to distinguish among closely related strains causing nosocomial infections. The software implementation is available at https://github.com/PROBIC/BIB
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    ABSTRACT: Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bac-teraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high-and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission , highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and trans-missibility are critical for understanding the multifaceted nature of bacterial virulence. Author Summary Global efforts to counter the growing problem of antibiotic resistance and develop alternative treatment strategies rely on a fuller understanding of when and why opportunistic
    PLoS Biology 10/2015; 13(9). DOI:10.1371/journal.pbio.1002229 · 9.34 Impact Factor
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    ABSTRACT: Orientia tsutsugamushi is the causative agent of scrub typhus, a disease transmitted by Leptotrombidium mites which is responsible for a severe and under-reported public health burden throughout Southeast Asia. Here we use multilocus sequence typing (MLST) to characterize 74 clinical isolates from three geographic locations in the Lao PDR (Laos), and compare them with isolates described from Udon Thani, northeast Thailand. The data confirm high levels of diversity and recombination within the natural O. tsutsugamushi population, and a rate of mixed infection of ~8%. We compared the relationships and geographical structuring of the strains and populations using allele based approaches (eBURST), phylogenetic approaches, and by calculating F-statistics (FST). These analyses all point towards low levels of population differentiation between isolates from Vientiane and Udon Thani, cities which straddle the Mekong River which defines the Lao/Thai border, but with a very distinct population in Salavan, southern Laos. These data highlight how land use, as well as the movement of hosts and vectors, may impact on the epidemiology of zoonotic infections.
    PLoS Neglected Tropical Diseases 08/2015; 9(8):e0004024. DOI:10.1371/journal.pntd.0004024 · 4.45 Impact Factor
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    ABSTRACT: In North America, Lyme disease (LD) is a tick-borne zoonosis caused by the spirochaete bacterium Borrelia burgdorferi sensu stricto (s.s.), which is maintained by wildlife. Tick vectors and bacteria are currently spreading into Canada and causing increasing numbers of cases of LD in humans and raising a pressing need for public health responses. There is no vaccine and LD prevention depends on knowing who is at risk and informing them how to protect themselves from infection. Recently, it was found in the USA that some strains of B. burgdorferi s.s. cause severe disease, whereas others cause mild, self-limiting disease. While many strains occurring in the USA also occur in Canada, strains in some parts of Canada are different than those in the USA. We therefore a a need to identify which strains specific to Canada can cause severe disease, and to characterize their geographic distribution to determine which Canadians are particularly at risk. In this review, we summarise the history of emergence of LD in North America, our current knowledge of B. burgdorferi s.s. diversity, its intriguing origins in the ecology and evolution of the bacterium, and its importance for the epidemiology, and clinical and laboratory diagnosis of LD. We propose methods for investigating associations between B. burgdorferi s.s. diversity, ecology and pathogenicity, and developing predictive tools to guide public health interventions. We also highlight the emergence of B. burgdorferi s.s. in Canada as a unique opportunity for exploring the evolutionary aspects of tick-borne pathogen emergence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Applied and Environmental Microbiology 08/2015; 81(21). DOI:10.1128/AEM.01671-15 · 3.67 Impact Factor
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    ABSTRACT: Genomic and transcriptomics analyses have revealed human head and body lice to be almost genetically identical; although con-specific, they nevertheless occupy distinct ecological niches and have differing feeding patterns. Most importantly, while head lice are not known to be vector competent, body lice can transmit three serious bacterial diseases; epidemictyphus, trench fever and relapsing fever. In order to gain insights into the molecular bases for these differences, we analysed alternative splicing (AS) using next generation sequencing data for one strain of head lice and one strain of body lice. We identified a total of 3,598 AS events which were head or body lice specific. Exon skipping AS events were overrepresented among both head and body lice, while intron retention events were underrepresented in both. However, both the enrichment of exon skipping and the underrepresentation of intron retention are significantly stronger in body lice compared to head lice. Genes containing body louse specific AS events were found to be significantly enriched for functions associated with development of the nervous system, salivary gland, trachea and ovarian follicle cells, as well as regulation of transcription. In contrast, no functional categories were overrepresented among genes with head louse specific AS events. Together, our results constitute the first evidence for transcript pool differences in head and body lice, providing insights into molecular adaptations that enabled human lice to adapt to clothing, and representing a powerful illustration of the pivotal role AS can play in functional adaptation. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Molecular Biology and Evolution 07/2015; 32(10). DOI:10.1093/molbev/msv151 · 9.11 Impact Factor
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    ABSTRACT: The opportunistic pathogens Staphylococcus aureus and Staphylococcus epidermidis represent major causes of severe nosocomial infection, and are associated with high levels of mortality and morbidity worldwide. These species are both common commensals on the human skin and in the nasal pharynx, but are genetically distinct, differing at 24% average nucleotide divergence in 1,478 core genes. To better understand the genome dynamics of these ecologically similar staphylococcal species, we carried out a comparative analysis of 324 S. aureus and S. epidermidis genomes, including 83 novel S. epidermidis sequences. A reference pan-genome approach and whole genome multilocus-sequence typing revealed that around half of the genome (1,478 genes) was shared between the species. Based on a BratNextGen analysis, homologous recombination was found to have impacted on 40% of the core genes in S. epidermidis, but on only 24% of the core genes in S. aureus. Homologous recombination between the species is rare, with a maximum of 9 gene alleles shared between any two S. epidermidis and S. aureus isolates. In contrast, considerable interspecies admixture is noted in mobile elements, in particular genes associated with the SaPIn1 pathogenicity island, metal detoxification, and the methicillin-resistance island SCCmec. Our data and analysis provide a context for considering the nature of recombinational boundaries between S. aureus and S. epidermidis and, the selective forces that influence realized recombination between these species. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Genome Biology and Evolution 04/2015; 7(5). DOI:10.1093/gbe/evv066 · 4.23 Impact Factor
  • Santiago Castillo-Ramirez · Edward J. Feil ·

    Molecular Medical Microbiology, 01/2015: pages 337-345; , ISBN: 9780123971692
  • S Mechai · G Margos · E J Feil · L R Lindsay · N H Ogden ·
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    ABSTRACT: Lyme disease, caused by the bacterium Borrelia burgdorferi sensu stricto, is an emerging zoonotic disease in Canada and is vectored by the blacklegged tick Ixodes scapularis. Here we used Bayesian analyses of Sequence Types (STs), determined by Multi-Locus Sequence Typing (MLST), to investigate the phylogeography of B. burgdorferi populations in southern Canada and the USA by analysing MLST data from 564 B. burgdorferi-positive samples collected in surveillance. A total of 107 Canadian samples from field sites were characterised as part of this study, and these data were combined with existing MLST data for samples from the USA and Canada. Only 17% of STs were common between both countries while 49% occurred only in the USA, and 34% occurred only in Canada. However, STs in southeastern Ontario and southwestern Quebec were typically identical to those in northeastern USA, suggesting a recent introduction into this region from the USA. In contrast, STs in other locations in Canada (the Maritimes; Long Point, Ontario; and southeastern Manitoba) were frequently unique to those locations, but were putative descendants of STs previously recorded in the USA. The picture in Canada is consistent with relatively recent introductions from multiple refugial populations in the USA. These data thus point to a geographic pattern of populations of B. burgdorferi in North America that may be more complex than simply comprising Northeast, Midwest and Californian groups. We speculate that this reflects the complex ecology and spatial distribution of key reservoir hosts. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Applied and Environmental Microbiology 12/2014; 81(4). DOI:10.1128/AEM.03730-14 · 3.67 Impact Factor
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    ABSTRACT: Microbial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen's evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate's toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen.
    Genome Research 04/2014; 24(5). DOI:10.1101/gr.165415.113 · 14.63 Impact Factor
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    ABSTRACT: Melissococcus plutonius is the causative agent of European foulbrood (EFB), which is a serious brood disease of the European honey bee (Apis mellifera). EFB remains a threat because of a poor understanding of disease epidemiology. We used a recently published multi-locus sequence typing method to characterise 206 M. plutonius isolates recovered from outbreaks in England and Wales over the course of 2 years. We detected 15 different sequence types (STs), which were resolved by eBURST and phylogenetic analysis into three clonal complexes (CCs) 3, 12 and 13. Single and double locus variants within CC3 were the most abundant and widespread genotypes, accounting for 85% of the cases. In contrast, CCs 12 and 13 were rarer and predominantly found in geographical regions of high sampling intensity, consistent with a more recent introduction and localised spread. K-function analysis and interpoint distance tests revealed significant geographical clustering in five common STs, but pointed to different dispersal patterns between STs. We noted that CCs appeared to vary in pathogenicity and that infection caused by the more pathogenic variants is more likely to lead to honey bee colony destruction, as opposed to treatment. The importance of these findings for improving our understanding of disease aetiology and control are discussed.The ISME Journal advance online publication, 6 March 2014; doi:10.1038/ismej.2014.20.
    The ISME Journal 03/2014; 8(8). DOI:10.1038/ismej.2014.20 · 9.30 Impact Factor
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    ABSTRACT: The hard tick Ixodes ricinus is the principal vector of Lyme borreliosis (LB) group spirochaetes in Europe, but it also transmits a large number of other microbial pathogens that are of importance to animal and human health. Here, we characterise geographically distinct populations of this important ectoparasite based on multilocus sequence typing (MLST) of multiple mitochondrial (mt) genes (mtMLST). Internal fragments of approximately 500bp were amplified and sequenced for 6 protein-encoding and ribosomal genes (atp6, coi, coii, coiii, cytB, and 12s). The samples analysed consisted of 506 questing nymphs collected in Britain and Latvia in 2006-2008 and in Latvia in 2002. Although little genetic structure has previously been observed in I. ricinus ticks among Europe, our data could clearly differentiate these 2 populations. Here, we argue that this novel scheme provides additional phylogenetic resolution which is important for understanding the genetic and geographic structure of I. ricinus populations. This in turn will benefit monitoring and management of tick-borne diseases.
    Ticks and Tick-borne Diseases 12/2013; 5(2). DOI:10.1016/j.ttbdis.2013.10.001 · 2.72 Impact Factor
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    ABSTRACT: Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum, is a bacterial disease of fish, which is both geographically widespread and difficult to control. Previously, application of various molecular typing methods has failed to reliably discriminate between R. salmoninarum isolates originating from different host species and geographic areas. The current study aimed to utilize multilocus variable number tandem repeats (VNTR) to investigate inter-strain variation of R. salmoninarum to establish whether host-specific populations exist in Atlantic salmon and rainbow trout respectively. Such information would be valuable in risk assessment of transmission of R. salmoninarum in a multispecies aquaculture environment. The present analysis utilizing sixteen VNTRs distinguished 17 different haplotypes amongst 41 R. salmoninarum isolates originating from Atlantic salmon and rainbow trout in Scotland, Norway and the US. The VNTR typing system revealed two well supported groups of R. salmoninarum haplotypes. The first group included R. salmoninarum isolates originating from both Atlantic salmon and rainbow trout circulating in Scottish and Norwegian aquaculture, in addition to the type strain ATCC33209T originating from Chinook salmon in North America. The second group comprised isolates found exclusively in Atlantic salmon, of mainly wild origin, including isolates NCIB1114 and NCIB1116 associated with the original Dee disease in Scotland. The present study confirmed that VNTR analysis can be successfully applied to discriminate R. salmoninarum strains. There was no clear distinction between isolates originating from Atlantic salmon and rainbow trout as several haplotypes in group 1 clustered together R. salmoninarum isolates from both species. These findings indicate a potential exchange of pathogens between Atlantic salmon and rainbow trout in Scottish and Norwegian aquaculture during the last 20 years. In a scenario of expansion of rainbow trout farming into the marine environment, appropriate biosecurity measures to minimize disease occurrence are advised. The present results also suggest that R. salmoninarum isolates circulating in European aquaculture over the last 20 years are genetically distant to the wild strains originally causing BKD in the rivers Dee and Spey.
    BMC Microbiology 12/2013; 13(1):285. DOI:10.1186/1471-2180-13-285 · 2.73 Impact Factor
  • Santiago Castillo-Ramírez · Edward J. Feil ·
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    ABSTRACT: The rapid development of sequencing technology over recent years has both transformed molecular epidemiological surveillance and provided unprecedented detail concerning the molecular evolutionary processes occurring over very short time scales in bacterial pathogens. Here we review recent developments, with an emphasis on the application of next-generation sequencing platforms to understand the spread and diversification of methicillin-resistant Staphylococcus aureus (MRSA). We discuss how these datasets may provide information on transmission dynamics at different epidemiological scales, but also consider methods to gauge the strength of purifying selection acting on populations and subpopulations, and how this is likely to intersect with the ecology or epidemiology of different species or clones. We also discuss how these datasets are shedding light on other evolutionary properties of bacteria, such as genomic base composition, recombination, and mutation rate.
    The Prokaryotes, 12/2013: pages 255-266; , ISBN: 978-3-642-30193-3
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    ABSTRACT: Renibacterium salmoninarum is the causative agent of bacterial kidney disease, a major pathogen of salmonid fish species worldwide. Very low levels of intra-species genetic diversity have hampered efforts to understand the transmission dynamics and recent evolutionary history of this Gram-positive bacterium. We exploited recent advances in the next-generation sequencing technology to generate genome-wide single-nucleotide polymorphism (SNP) data from 68 diverse R. salmoninarum isolates representing broad geographical and temporal ranges and different host species. Phylogenetic analysis robustly delineated two lineages (lineage 1 and lineage 2); futhermore, dating analysis estimated that the time to the most recent ancestor of all the isolates is 1239 years ago (95% credible interval (CI) 444-2720 years ago). Our data reveal the intercontinental spread of lineage 1 over the last century, concurrent with anthropogenic movement of live fish, feed and ova for aquaculture purposes and stocking of recreational fisheries, whilst lineage 2 appears to have been endemic in wild Eastern Atlantic salmonid stocks before commercial activity. The high resolution of the SNP-based analyses allowed us to separate closely related isolates linked to neighboring fish farms, indicating that they formed part of single outbreaks. We were able to demonstrate that the main lineage 1 subgroup of R. salmoninarum isolated from Norway and the UK likely represent an introduction to these areas ∼40 years ago. This study demonstrates the promise of this technology for analysis of micro and medium scale evolutionary relationships in veterinary and environmental microorganisms, as well as human pathogens.The ISME Journal advance online publication, 31 October 2013; doi:10.1038/ismej.2013.186.
    The ISME Journal 10/2013; 8(4). DOI:10.1038/ismej.2013.186 · 9.30 Impact Factor
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    ABSTRACT: Background Staphylococcus aureus exhibits tropisms to many distinct animal hosts. While spillover events can occur wherever there is an interface between host species, changes in host tropism only occur with the establishment of sustained transmission in the new host species, leading to clonal expansion. Although the genomic variation underpinning adaptation in S. aureus genotypes infecting bovids and poultry has been well characterized the frequency of switches from one host to another remains obscure. We sought to identify sustained switches in host tropism in the S. aureus population, both anthroponotic and zoonotic, and their distribution over the species phylogeny. Methodologies/Results We have used a sample of 3042 isolates, representing 696 distinct MLST genotypes, from a well-established database (www.mlst.net). Using an empirical parsimony approach (AdaptML) we have investigated the distribution of switches in host association between both human and non-human (henceforth referred to as animal) hosts. We reconstructed a credible description of past events in the form of a phylogenetic tree; the nodes and leaves of which are statistically associated with either human or animal habitats, estimated from extant host-association and the degree of sequence divergence between genotypes. We identified 15 likely historical switching events; 13 anthroponoses and two zoonoses. Importantly, we identified two human-associated clade candidates (CC25 and CC59) that have arisen from animal-associated ancestors; this demonstrates that a human-specific lineage can emerge from an animal host. We also highlight novel rabbit-associated genotypes arising from a human ancestor. Conclusions S. aureus is an organism with the capacity to switch into and adapt to novel hosts, even after long periods of isolation in a single host species. Based on this evidence, animal-adapted S. aureus lineages exhibiting resistance to antibiotics must be considered a major threat to public health, as they can adapt to the human population.
    PLoS ONE 05/2013; 8(5):e62369. DOI:10.1371/journal.pone.0062369 · 3.23 Impact Factor
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    ABSTRACT: Genotyping of Ixodes scapularis Say (Acari: Ixodidae) ticks could enhance understanding of the occurrence and genotypes of I. scapularis-borne pathogens. We investigated the utility of mitochondrial (mt) Cytochrome C Oxidase subunit I gene (cox1) sequences as a tool for understanding the population structure of I. scapularis collected in Canada, where we also investigated the geographic occurrence of different cox1 haplotypes. Sequences obtained from 414 ticks were one of 55 unique haplotypes, most of which grouped into one of six clades. Demographic analysis suggested that cox1 sequences have haplotype and nucleotide diversity comparable to other mt genes. All haplotypes were connected in a single minimum spanning network tree. Despite low fixation index values there were significant differences in the frequency of occurrence of haplotypes of different clades among four geographic regions: 1) Alberta to western Ontario, 2) eastern Ontario, 3) Quebec, and 4) Atlantic Provinces; suggesting that cox1 sequences could reveal population structure differences between I. scapularis in geographically separated populations of northeastern and midwestern North America. Spatial clusters of ticks of the same haplotype identified in regions of southern Quebec and southern Ontario where I. scapularis is invading were consistent with population bottlenecks associated with founder events. These findings suggest that cox1 sequences are useful for the study of I. scapularis population structure, are of sufficient diversity that spatial analyses of haplotypes can be used to identify where I. scapularis is emerging in southern Canada, and may be useful for exploring differences between northeastern and midwestern populations of I. scapularis.
    Journal of Medical Entomology 05/2013; 50(3):560-70. DOI:10.1603/ME12178 · 1.95 Impact Factor
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    ABSTRACT: Insect pollinators of crops and wild plants are under threat globally and their decline or loss could have profound economic and environmental consequences. Here, we argue that multiple anthropogenic pressures – including land-use intensification, climate change, and the spread of alien species and diseases – are primarily responsible for insect-pollinator declines. We show that a complex interplay between pressures (eg lack of food sources, diseases, and pesticides) and biological processes (eg species dispersal and interactions) at a range of scales (from genes to ecosystems) underpins the general decline in insect-pollinator populations. Interdisciplinary research on the nature and impacts of these interactions will be needed if human food security and ecosystem function are to be preserved. We highlight key areas that require research focus and outline some practical steps to alleviate the pressures on pollinators and the pollination services they deliver to wild and crop plants.
    Frontiers in Ecology and the Environment 04/2013; DOI:10.1890/120126 · 7.44 Impact Factor

Publication Stats

12k Citations
817.76 Total Impact Points


  • 2015
    • Swansea University
      • Institute of Life Science "ILS"
      Swansea, Wales, United Kingdom
  • 2001-2015
    • University of Bath
      • Department of Biology and Biochemistry
      Bath, England, United Kingdom
  • 1999-2009
    • University of Oxford
      • • Nuffield Department of Clinical Medicine
      • • Department of Zoology
      Oxford, England, United Kingdom
  • 2008
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • Mahidol University
      • Faculty of Tropical Medicine
      Bangkok, Bangkok, Thailand
  • 2007
    • University of Delaware
      • Department of Biological Sciences
      Delaware, United States
  • 2003-2004
    • Imperial College London
      • Department of Infectious Disease Epidemiology
      Londinium, England, United Kingdom
  • 1995-1998
    • University of Sussex
      Brighton, England, United Kingdom