ORCID Profile
0000-0001-6376-5121
Current Organisations
University of Arizona
,
Chiang Mai University
,
University of Oxford
,
Chiang Mai University Faculty of Associated Medical Sciences
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Publisher: Cold Spring Harbor Laboratory
Date: 24-08-2021
DOI: 10.1101/2021.08.24.457495
Abstract: Horizontal gene transfer (HGT) can allow traits that have evolved in one bacterial species to transfer to another. This has potential to rapidly promote new adaptive trajectories such as zoonotic transfer or antimicrobial resistance. However, for this to occur requires gaps to align in barriers to recombination within a given time frame. Chief among these barriers is the physical separation of species with distinct ecologies in separate niches. Within the genus C ylobacter there are species with ergent ecologies, from rarely isolated single host specialists to multi-host generalist species that are among the most common global causes of human bacterial gastroenteritis. Here, by characterising these contrasting ecologies, we can quantify HGT among sympatric and allopatric species in natural populations. Analysing recipient and donor population ancestry among genomes from 30 C ylobacter species we show that cohabitation in the same host can lead to a 6-fold increase in HGT between species. This accounts for up to 30% of all SNPs within a given species and identifies highly recombinogenic genes with functions including host adaptation and antimicrobial resistance. As described in some animal and plant species, ecological factors are a major evolutionary force for speciation in bacteria and changes to the host landscape can promote partial convergence of distinct species through HGT.
Publisher: Microbiology Society
Date: 03-11-2022
Abstract: Streptococcus suis is a leading cause of bacterial meningitis in South-East Asia, with frequent zoonotic transfer to humans associated with close contact with pigs. A small number of invasive lineages are responsible for endemic infection in the swine industry, causing considerable global economic losses. A lack of surveillance and a rising trend in clinical treatment failure has raised concerns of growing antimicrobial resistance (AMR) among invasive S. suis . Gene flow between healthy and disease isolates is poorly understood and, in this study, we s le and sequence a collection of isolates predominantly from healthy pigs in Chiang Mai province, Northern Thailand. Pangenome characterization identified extensive genetic ersity and frequent AMR carriage in isolates from healthy pigs. Multiple AMR genes were identified, conferring resistance to aminoglycosides, lincosamides, tetracycline and macrolides. All isolates were non-susceptible to three or more different antimicrobial classes, and 75 % of non-serotype 2 isolates were non-susceptible to six or more classes (compared to 37.5 % of serotype 2 isolates). AMR genes were found on integrative and conjugative elements previously observed in other species, suggesting a mobile gene pool that can be accessed by invasive disease isolates. This article contains data hosted by Microreact .
Publisher: Oxford University Press (OUP)
Date: 04-2017
DOI: 10.1093/GBE/EVX037
Publisher: Public Library of Science (PLoS)
Date: 15-03-2016
Publisher: Cold Spring Harbor Laboratory
Date: 05-06-2018
DOI: 10.1101/332544
Abstract: Determining the composition of bacterial communities beyond the level of a genus or species is challenging because of the considerable overlap between genomes representing close relatives. Here, we present the mSWEEP method for identifying and estimating the relative abundances of bacterial lineages from plate sweeps of enrichment cultures. mSWEEP leverages biologically grouped sequence assembly databases, applying probabilistic modelling, and provides controls for false positive results. Using sequencing data from major pathogens, we demonstrate significant improvements in lineage quantification and detection accuracy. Our method facilitates investigating cultures comprising mixtures of bacteria, and opens up a new field of plate sweep metagenomics.
Publisher: Microbiology Society
Date: 07-2019
Abstract: Reference and type strains of well-known bacteria have been a cornerstone of microbiology research for decades. The sharing of well-characterized isolates among laboratories has run in parallel with research efforts and enhanced the reproducibility of experiments, leading to a wealth of knowledge about trait variation in different species and the underlying genetics. C ylobacter jejuni strain NCTC 11168, deposited at the National Collection of Type Cultures in 1977, has been adopted widely as a reference strain by researchers worldwide and was the first C ylobacter for which the complete genome was published (in 2000). In this study, we collected 23 C . jejuni NCTC 11168 reference isolates from laboratories across the UK and compared variation in simple laboratory phenotypes with genetic variation in sequenced genomes. Putatively identical isolates, identified previously to have aberrant phenotypes, varied by up to 281 SNPs (in 15 genes) compared to the most recent reference strain. Isolates also display considerable phenotype variation in motility, morphology, growth at 37 °C, invasion of chicken and human cell lines, and susceptibility to icillin. This study provides evidence of ongoing evolutionary change among C. jejuni isolates as they are cultured in different laboratories and highlights the need for careful consideration of genetic variation within laboratory reference strains. This article contains data hosted by Microreact .
Publisher: eLife Sciences Publications, Ltd
Date: 03-02-2022
Publisher: Public Library of Science (PLoS)
Date: 21-04-2016
Publisher: F1000 Research Ltd
Date: 30-01-2020
DOI: 10.12688/WELLCOMEOPENRES.15639.1
Abstract: Determining the composition of bacterial communities beyond the level of a genus or species is challenging because of the considerable overlap between genomes representing close relatives. Here, we present the mSWEEP pipeline for identifying and estimating the relative sequence abundances of bacterial lineages from plate sweeps of enrichment cultures. mSWEEP leverages biologically grouped sequence assembly databases, applying probabilistic modelling, and provides controls for false positive results. Using sequencing data from major pathogens, we demonstrate significant improvements in lineage quantification and detection accuracy. Our pipeline facilitates investigating cultures comprising mixtures of bacteria, and opens up a new field of plate sweep metagenomics.
Publisher: Wiley
Date: 31-12-2014
DOI: 10.1111/MEC.13001
Abstract: Environmental pollution often accompanies the expansion and urbanization of human populations where sewage and wastewaters commonly have an impact on the marine environments. Here, we explored the potential for faecal bacterial pathogens, of anthropic origin, to spread to marine wildlife in coastal areas. The common zoonotic bacterium C ylobacter was isolated from grey seals (Halichoerus grypus), an important sentinel species for environmental pollution, and compared to isolates from wild birds, agricultural sources and clinical s les to characterize possible transmission routes. C ylobacter jejuni was present in half of all grey seal pups s led (24/50 dead and 46/90 live pups) in the breeding colony on the Isle of May (Scotland), where it was frequently associated with histological evidence of disease. Returning yearling animals (19/19) were negative for C. jejuni suggesting clearance of infection while away from the localized colony infection source. The genomes of 90 isolates from seals were sequenced and characterized using a whole-genome multilocus sequence typing (MLST) approach and compared to 192 published genomes from multiple sources using population genetic approaches and a probabilistic genetic attribution model to infer the source of infection from MLST data. The strong genotype-host association has enabled the application of source attribution models in epidemiological studies of human c ylobacteriosis, and here assignment analyses consistently grouped seal isolates with those from human clinical s les. These findings are consistent with either a common infection source or direct transmission of human c ylobacter to grey seals, raising concerns about the spread of human pathogens to wildlife marine sentinel species in coastal areas.
Publisher: F1000 Research Ltd
Date: 08-10-2021
DOI: 10.12688/WELLCOMEOPENRES.15639.2
Abstract: Determining the composition of bacterial communities beyond the level of a genus or species is challenging because of the considerable overlap between genomes representing close relatives. Here, we present the mSWEEP pipeline for identifying and estimating the relative sequence abundances of bacterial lineages from plate sweeps of enrichment cultures. mSWEEP leverages biologically grouped sequence assembly databases, applying probabilistic modelling, and provides controls for false positive results. Using sequencing data from major pathogens, we demonstrate significant improvements in lineage quantification and detection accuracy. Our pipeline facilitates investigating cultures comprising mixtures of bacteria, and opens up a new field of plate sweep metagenomics.
Publisher: Cold Spring Harbor Laboratory
Date: 18-04-2019
DOI: 10.1101/591701
Abstract: Reference and type strains of well-known bacteria have been a cornerstone of microbiology research for decades. The sharing of well-characterised isolates among laboratories has parallelised research efforts and enhanced the reproducibility of experiments, leading to a wealth of knowledge about trait variation in different species and the underlying genetics. C ylobacter jejuni strain NCTC 11168, deposited at the National Collection of Type Cultures in 1977, has been adopted widely as a reference strain by researchers worldwide and was the first C ylobacter for which the complete genome was published (in 2000). In this study, we collected 23 C. jejuni NCTC 11168 reference isolates from laboratories across the UK and compared variation in simple laboratory phenotypes with genetic variation in sequenced genomes. Putatively identical isolates identified previously to have aberrant phenotypes varied by up to 281 SNPs (in 15 genes) compared to the most recent reference strain. Isolates also display considerable phenotype variation in motility, morphology, growth at 37°C, invasion of chicken and human cell lines and susceptibility to icillin. This study provides evidence of ongoing evolutionary change among C. jejuni isolates as they are cultured in different laboratories and highlights the need for careful consideration of genetic variation within laboratory reference strains. In this paper, we comment on the changing role of laboratory reference strains. While the model organism allows basic comparison within and among laboratories, it is important to remember the effect even small differences in isolate genomes can have on the validity and reproducibility of experimental work. We quantify differences in 23 reference C ylobacter genomes and compare them with observable differences in common laboratory phenotypes. Short read data are archived on the NCBI SRA associated with BioProject accession PRJNA517467 ( ioproject/PRJNA517467 ). All assembled genomes are also available on FigShare (doi: 10.6084/m9.figshare.7849268). Phylogeny visualised on microreact: roject/NCTC11168 . Short read data are archived on the NCBI SRA repository, associated with BioProject accession PRJNA517467 ( ioproject/PRJNA517467 Table S1 ). The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
Publisher: Cold Spring Harbor Laboratory
Date: 17-06-2021
DOI: 10.1101/2021.06.17.447897
Abstract: Streptococcus suis is a leading cause of bacterial meningitis in SE Asia, with frequent zoonotic transfer to humans associated with close contact with pigs. A small number of invasive lineages are responsible for endemic infection in the swine industry causing considerable global economic losses. A lack of surveillance and a rising trend in clinical treatment failure has raised concerns of growing antimicrobial resistance (AMR) among invasive S. suis . The source-sink dynamics between healthy and disease isolates is poorly understood and, in this study, we s le and sequence a collection of isolates predominantly from healthy pigs in Chiang Mai province, Northern Thailand. Pangenome comparisons with a selection of invasive serotype 2 isolates identified increased genetic ersity and more frequent AMR carriage in isolates from healthy pigs. Multiple antimicrobial resistance genes were identified conferring resistance to aminoglycosides, lincosamides, tetracycline and macrolides. All isolates were non-susceptinle to three or more different antimicrobial classes, and 75% of non-serotype 2 isolates were non-susceptible to 6 or more classes (compared to 37.5% of serotype 2 isolates). Antimicrobial resistance genes were found on integrative and conjugative elements (ICE) previously observed in other species, suggesting mobile gene pool which can be accessed by invasive disease isolates. The zoonotic pathogen Streptococcus suis causes respiratory disease in pigs and is among the most common causative agents of human clinical bacterial meningitis in SE Asia. We collected isolates from farmed healthy pigs in Northern Thailand, representing a source population from which invasive isolates have recently emerged – linked to the pork production industry. Pangenome characterisation of the isolates revealed a reservoir of genetic ersity and antimicrobial resistance suggesting that One Health approaches may be beneficial in tackling the increase in antimicrobial resistance.
Publisher: MDPI AG
Date: 12-03-2018
DOI: 10.3390/MIN8030114
Publisher: Public Library of Science (PLoS)
Date: 10-08-2020
Publisher: Springer Science and Business Media LLC
Date: 28-11-2018
DOI: 10.1038/S41467-018-07368-7
Abstract: Some of the most common infectious diseases are caused by bacteria that naturally colonise humans asymptomatically. Combating these opportunistic pathogens requires an understanding of the traits that differentiate infecting strains from harmless relatives. Staphylococcus epidermidis is carried asymptomatically on the skin and mucous membranes of virtually all humans but is a major cause of nosocomial infection associated with invasive procedures. Here we address the underlying evolutionary mechanisms of opportunistic pathogenicity by combining pangenome-wide association studies and laboratory microbiology to compare S. epidermidis from bloodstream and wound infections and asymptomatic carriage. We identify 61 genes containing infection-associated genetic elements (k-mers) that correlate with in vitro variation in known pathogenicity traits (biofilm formation, cell toxicity, interleukin-8 production, methicillin resistance). Horizontal gene transfer spreads these elements, allowing ergent clones to cause infection. Finally, Random Forest model prediction of disease status (carriage vs. infection) identifies pathogenicity elements in 415 S. epidermidis isolates with 80% accuracy, demonstrating the potential for identifying risk genotypes pre-operatively.
Publisher: Springer Science and Business Media LLC
Date: 22-03-2021
DOI: 10.1038/S41467-021-22238-5
Abstract: A Correction to this paper has been published: 0.1038/s41467-021-22238-5
Publisher: Public Library of Science (PLoS)
Date: 27-03-2014
Publisher: Wiley
Date: 04-2018
DOI: 10.1111/MEC.14546
Publisher: Springer Science and Business Media LLC
Date: 03-02-2021
DOI: 10.1038/S41467-021-20988-W
Abstract: Chickens are the most common birds on Earth and colibacillosis is among the most common diseases affecting them. This major threat to animal welfare and safe sustainable food production is difficult to combat because the etiological agent, avian pathogenic Escherichia coli (APEC), emerges from ubiquitous commensal gut bacteria, with no single virulence gene present in all disease-causing isolates. Here, we address the underlying evolutionary mechanisms of extraintestinal spread and systemic infection in poultry. Combining population scale comparative genomics and pangenome-wide association studies, we compare E. coli from commensal carriage and systemic infections. We identify phylogroup-specific and species-wide genetic elements that are enriched in APEC, including pathogenicity-associated variation in 143 genes that have erse functions, including genes involved in metabolism, lipopolysaccharide synthesis, heat shock response, antimicrobial resistance and toxicity. We find that horizontal gene transfer spreads pathogenicity elements, allowing ergent clones to cause infection. Finally, a Random Forest model prediction of disease status (carriage vs. disease) identifies pathogenic strains in the emergent ST-117 poultry-associated lineage with 73% accuracy, demonstrating the potential for early identification of emergent APEC in healthy flocks.
Publisher: Cold Spring Harbor Laboratory
Date: 05-2020
DOI: 10.1101/2020.04.26.20075689
Abstract: C ylobacter is the leading bacterial cause of gastroenteritis worldwide and its incidence is especially high in low- and middle-income countries (LMIC). Disease epidemiology in LMICs is different compared to high income countries like the USA or in Europe. Children in LMICs commonly have repeated and chronic infections even in the absence of symptoms, which can lead to deficits in early childhood development. In this study, we sequenced and characterized C. jejuni (n=62) from a longitudinal cohort study of children under the age of 5 with and without diarrheal symptoms, and contextualized them within a global C. jejuni genome collection. Epidemiological differences in disease presentation were reflected in the genomes, specifically by the absence of some of the most common global disease-causing lineages. As in many other countries, poultry-associated strains were a major source of human infection but almost half of local disease cases (15 of 31) were attributable to genotypes that are rare outside of Peru. Asymptomatic infection was not limited to a single (or few) human adapted lineages but resulted from phylogenetically ergent strains suggesting an important role for host factors in the cryptic epidemiology of c ylobacteriosis in LMICs. C ylobacter is the leading bacterial cause of gastroenteritis worldwide and despite high incidence in low- and middle-income countries (LMICs), where infection can be fatal, culture based isolation is rare and the genotypes responsible for disease have not broadly been identified. The epidemiology of disease is different to that in high income countries, where sporadic infection associated with contaminated food consumption typically leads to acute gastroenteritis. In some LMICs infection is endemic among children and common asymptomatic carriage is associated with malnutrition, attenuated growth in early childhood, and poor cognitive and physical development. Here, we sequenced the genomes of isolates s led from children in the Peruvian Amazon to investigate genotypes associated with varying disease severity and the source of infection. Among the common globally circulating genotypes and local genotypes rarely seen before, no single lineage was responsible for symptomatic or asymptomatic infection – suggesting an important role for host factors. However, consistent with other countries, poultry-associated strains were a major source of infection. This genomic surveillance approach, that integrates microbial ecology with population based studies in humans and animals, has considerable potential for describing cryptic epidemiology in LMICs and will inform work to improve infant health worldwide.
Publisher: eLife Sciences Publications, Ltd
Date: 22-02-2022
DOI: 10.7554/ELIFE.73552
Abstract: Horizontal gene transfer (HGT) can allow traits that have evolved in one bacterial species to transfer to another. This has potential to rapidly promote new adaptive trajectories such as zoonotic transfer or antimicrobial resistance. However, for this to occur requires gaps to align in barriers to recombination within a given time frame. Chief among these barriers is the physical separation of species with distinct ecologies in separate niches. Within the genus C ylobacter, there are species with ergent ecologies, from rarely isolated single-host specialists to multihost generalist species that are among the most common global causes of human bacterial gastroenteritis. Here, by characterizing these contrasting ecologies, we can quantify HGT among sympatric and allopatric species in natural populations. Analyzing recipient and donor population ancestry among genomes from 30 C ylobacter species, we show that cohabitation in the same host can lead to a six-fold increase in HGT between species. This accounts for up to 30% of all SNPs within a given species and identifies highly recombinogenic genes with functions including host adaptation and antimicrobial resistance. As described in some animal and plant species, ecological factors are a major evolutionary force for speciation in bacteria and changes to the host landscape can promote partial convergence of distinct species through HGT.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: Thailand
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ben Pascoe.