Biology subjects

Chattaway, M. A.

Publications and source records attributed to Chattaway, M. A..

9 recordsLinked to original sources

bioRxiv2026

Population analysis and host-disease associations of Shiga toxin-producing Escherichia coli from various sources across eleven European countries using whole genome sequencing

Shiga toxin-producing Escherichia coli (STEC) are important foodborne pathogens, able to cause severe disease in humans. In the DiSCoVeR project (https://onehealthejp.eu/jrp-discover/) a STEC inventory from human and non-human sources from 11 European countries was set up and [≥] 3500 strains were sequenced to perform comparative genomics analysis. We used this dataset to assess STEC population structure and to investigate potential associations between genomic features, host reservoirs and symptoms. Most STEC isolates analysed by Whole Genome Sequencing (WGS) in this study were collected between years 2010-2020. An ad hoc pipeline was deployed for a harmonised characterization of the STEC in the database, allowing the determination of serotyping, stx gene subtyping, 7-loci MLST, virulotyping and cgMLST. The results were analysed with Principal Component Analysis (PCoA) in relation with isolation source to assess clustering of STEC subpopulations. When human STEC data were analysed, the PCoA revealed three distinct human STEC subpopulations (STEC_1, STEC_2 and STEC_3), which were further analysed for associations between genomic features, symptoms and variance. The non-human STEC showed a more dispersed distribution, except for one subpopulation with genes linked to specific host species, and some virulence profiles overlapping with the STEC_1 population. In conclusion, our analysis identified distinct STEC subpopulations from human cases, each characterized by specific genetic features and associated with varying proportions of severe disease outcomes. These findings provide novel insights supporting the risk assessment of STEC. Impact statement[This lay summary of your article should be no more than 200 words, and should a) provide a perspective of how this article adds to the literature in the field; b) identify breadth of interest/utility; and c) state the significance of output (incremental or step), in terms of relevance.] This study is based on the establishment of a One Health STEC genomes database, including sequences from isolates of different sources. Most of the isolates had been isolated in the ten-years time span 2010-2020, in 11 different countries, for surveillance and monitoring activities or specific surveys and research purposes. The final dataset included the whole genome sequencing of 3,418 STEC isolates, mainly from human cases of infections. The metadata included the host symptoms, where available, for human STEC strains and the animal source the strains had been isolated from. We set up a pipeline for the harmonized analysis of STEC WGS, called Discover, made available though ARIES webserver or GitHub. The analysis allowed a deep characterization of STEC strains circulating in Europe. We used this resource to assess STEC population structure and to investigate potential associations between genomic features, host reservoirs, and various symptoms associated with STEC infection by PCoA. This analysis highlighted the presence of subpopulation of human STEC associated with specific features. We provide new information useful for risk characterization, as well as a large dataset genome database and associated metadata compiled from STEC strains, representing a valuable resource for the scientific community, enabling further investigations into STEC diversity, evolution, source attribution and public health relevance. Data summaryThe authors confirm all supporting data, including sequence data accession numbers, code and protocols have been provided within the article or through supplementary data files. One supplementary method and five supplementary tables are available with the online version of this article

genomics↗

bioRxiv2026

Salmonella Genomic Markers for Risk to Food Safety

Foodborne non-typhoidal Salmonella remains a major public health concern, yet many isolates recovered through food surveillance are not associated with human illness. To investigate whether genomic factors influence infection risk, we analysed whole-genome sequencing data from over 900 food and environmental isolates collected through UK Health Security Agency surveillance. Hierarchical clustering and comparative genomics identified distinct lineages associated with clinical cases, which were further contextualised using the global EnteroBase database. By combining pangenome and genome-wide association analyses, we identified distinct lineages within several serovars that differed in their association with human cases. In Salmonella Agona, all clinical isolates belonged to a single lineage carrying a highly conserved 7 kb marker that was absent from low-risk strains and demonstrated strong sensitivity and specificity across global datasets. This marker was located within a prophage closely related to the well-characterised Fels-2 phage and encodes a DNA invertase previously implicated in phase variation, a mechanism that promotes bacterial adaptability. Our findings indicate that infection risk can be structured at the lineage level and associated with mobile genomic elements, particularly prophages, that may contribute to environmental persistence and host adaptation. This work advances genomic surveillance from retrospective linkage towards mechanistic and predictive risk assessment, with direct relevance for supporting risk-based decision-making during outbreak investigations. IMPORTANCENot all strains found in food pose the same risk to human health, yet current surveillance systems generally treat them as equivalent hazards. We analysed over 900 genomes from food and environmental sources and found that human infection risk can be concentrated within specific genetic lineages rather than distributed across an entire serovar. In Salmonella Agona, we identified a highly conserved prophage-associated marker with strong sensitivity and specificity for infection-associated lineages. This marker was located within a prophage related to the well-characterised Fels-2 phage and encoded a DNA invertase previously associated to bacterial adaptation. These findings show how genome sequencing can move beyond outbreak detection to identify lineages with elevated public health relevance. Incorporating such information into surveillance programmes could improve risk-based decision-making, helping public health agencies prioritise investigations and interventions more effectively.

genomics↗

bioRxiv2025

Large-scale genomic characterisation of phage-plasmids in clinical Enterobacteriaceae isolates

The life cycle of certain bacteriophages involves their maintenance within the bacterial cell as extrachromosomal elements, complete with replication and partitioning systems. These "phage-plasmids" (P-Ps) are distributed widely among bacterial phyla but are not typically included during genomic surveillance studies, and previous reports do not consider the context of their host strain diversity. We recently identified a P1-like P-P carrying the blaCTX-M-15 resistance gene in Salmonella enterica serovar Typhi, prompting a subsequent investigation into the overall frequency of P-Ps among gastrointestinal bacteria under routine genomic surveillance within England. We expanded our study to include P-P groups known to be associated with Enterobacteriaceae (P1, D6, SSU5, N15) and scanned a collection of 66,856 genomes of diarrhoeagenic Escherichia spp., Shigella spp. and S. enterica. All four P-P groups were detected in our dataset, totalling 9% of E. coli and Shigella genomes and 2% of S. enterica genomes. A small subset harboured two distinct P-P groups. P1-like P-Ps, some of which carried a cytotoxic necrotising factor, were predominantly associated with Shiga toxin-producing E. coli strains of public health concern, including clonal complexes CC11 (O157:H7), CC29 (O26:H11) and CC165. In contrast, SSU5 group P-Ps were linked with multidrug-resistant lineages of both S. Typhi and Shigella sonnei. We found multiple antimicrobial resistance genes inserted into P-Ps via transposons, integrons and insertion sequences, and numerous defence/anti-defence systems. There was evidence of vertical transmission but also many links across species, time and geography, indicating that horizontal transfer is occurring regularly. Phage-plasmids are often described only as cryptic elements or not detected during genomic surveillance. We show that P-Ps are associated with clinically relevant lineages of human pathogens and can acquire accessory genes that may impact on disease severity and therefore should play a more prominent role in pathogen surveillance and epidemiology.

genomics↗

bioRxiv2024

Typhi Mykrobe: fast and accurate lineage identification and antimicrobial resistance genotyping directly from sequence reads for the typhoid fever agent Salmonella Typhi

BackgroundTyphoid fever results from systemic infection with Salmonella enterica serovar Typhi (Typhi) and causes 10 million illnesses annually. Disease control relies on prevention (water, sanitation, and hygiene interventions or vaccination) and effective antimicrobial treatment. Antimicrobial resistant (AMR) Typhi lineages have emerged and become established in many parts of the world. Knowledge of local pathogen populations informed by genomic surveillance, including of lineages (defined by the GenoTyphi scheme) and AMR determinants, is increasingly used to inform local treatment guidelines and to inform vaccination strategy. Current tools for genotyping Typhi require multiple read alignment or assembly steps and have not been validated for analysis of data generated with Oxford Nanopore Technologies (ONT) long-read sequencing devices. Here, we introduce Typhi Mykrobe, a command line software tool for rapid genotyping of Typhi lineages, AMR determinants, and plasmid replicons direct from sequencing reads. ResultsWe validated Typhi Mykrobe lineage genotyping by comparison with the current standard read mapping-based approach and demonstrated 99.8% concordance across nearly 13,000 genomes sequenced with Illumina platforms. For the few isolates with discordant calls, we show that Typhi Mykrobe results are better supported by the evidence from raw sequence read data than the results generated using the mapping-based approach. We also demonstrate 99.9% concordance for detection of AMR determinants compared with the current standard assembly-based approach, with similar results for plasmid marker detection. Typhi Mykrobe predicts clinical resistance categorisation (S/I/R) for eight drug classes, and we show strong agreement with phenotypic categorisations generated from reference laboratory minimum inhibitory concentration (MIC) data for n=1,572 Illumina-sequenced isolates (>99% agreement within one doubling dilution). We show strong concordance (>96% for genotype and >98% for AMR and plasmid) between calls made from ONT reads and those made from Illumina reads for isolates sequenced on both platforms (n =93 genomes). Typhi Mykrobe takes less than a minute per sample and is available at https://github.com/typhoidgenomics/genotyphi. ConclusionsTyphi Mykrobe provides rapid and sensitive genotyping of Typhi genomes direct from Illumina and ONT reads, although lower accuracy was observed for R9 ONT data. It demonstrated accurate assignment of GenoTyphi lineage, detection of AMR determinants and prediction of corresponding AMR phenotypes, and identification of plasmid replicons.

microbiology↗

bioRxiv2024

Global diversity and evolution of Salmonella Panama, an understudied serovar causing gastrointestinal and invasive disease worldwide: a genomic epidemiology study

BackgroundNontyphoidal Salmonella (NTS) is a globally important bacterial pathogen, typically associated with foodborne gastrointestinal infection. Some NTS serovars can also colonise normally sterile sites in humans to cause invasive NTS (iNTS) disease. One understudied Salmonella enterica serovar which is responsible for a significant number of cases of iNTS disease is Panama. Despite global dissemination, numerous outbreaks, and a reported association with iNTS disease, S. enterica serovar Panama (S. Panama) has not been investigated in detail. MethodsUsing combined epidemiological and whole genome sequencing data we analysed 836 S. Panama genomes derived from historical collections, national surveillance datasets, and publicly available data. The collection represents all inhabited continents and includes isolates collected between 1931 and 2019. Maximum likelihood and Bayesian phylodynamic approaches were used to determine population structure & evolutionary history, and to infer geo-temporal dissemination. A combination of different bioinformatic approaches utilising short-read and long-read data were used to characterise geographic and clade-specific trends in antimicrobial resistance (AMR), and genetic markers for invasiveness. FindingsWe identified the presence of multiple geographically linked S. Panama clades, and regional trends in antimicrobial resistance profiles. Most isolates were pan-susceptible to antibiotics and belonged to clades circulating in the United States of America, Latin America, and the Caribbean. Multidrug resistant (MDR) isolates in our collection belonged to two phylogenetic clades circulating in Europe and Asia/Oceania, which exhibited the highest invasiveness indices based on the conservation of 196 extra-intestinal predictor genes. InterpretationThis first large-scale phylogenetic analysis of S. Panama revealed important information about population structure, AMR, global ecology, and genetic markers of invasiveness of the identified genomic subtypes. Our findings provide an important baseline for understanding S. Panama infection in the future. The presence of MDR clades with an elevated invasiveness index should be monitored by ongoing surveillance as such clades may pose an increased public health risk. FundingThe project was supported by both a Global Challenges Research Fund (GCRF) data & resources grant BBS/OS/GC/000009D and the BBSRC Core Capability Grant to the Earlham Institute BB/CCG1720/1. JCDH received a Wellcome Trust Investigator award (grant number 222528/Z/21/Z). CVP was supported by the John Lennon Memorial Scholarship from the University of Liverpool and a Fee Bursary Award from the Institute of Integrative Biology at the University of Liverpool. FXW was awarded the Institut Pasteur; Sante publique France; the Fondation Le Roch-Les Mousquetaires; and the French governments Investissement dAvenir programme, Laboratoire dExcellence "Integrative Biology of Emerging Infectious Diseases" (grant number ANR-10-LABX-62-IBEID). MDS was supported by a BBSRC grant (KSB: BB/V009184/1). RJBengtsson was supported by an MRC grant (KSB: MR/R020787/1). RJBennett was supported by a BBSRC DTP (BB/M011186/1). DJI was supported by a National Health and Medical Research Council (NHMRC) Emerging Leadership Fellowship (GNT1195210). BPH was supported by NHMRC Leadership Fellowship (GNT1196103). KSB and EVR are affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections at University of Liverpool in partnership with the United Kingdom Health Security Agency, in collaboration with University of Warwick. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or UKHSA. MAC is affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) (NIHR200892) in Genomics and Enabling Data at University of Warwick in partnership with the UK Health Security Agency (UKHSA), in collaboration with Universities of Cambridge and Oxford. MAC is based at UKHSA. The views expressed are those of the author(s) and not necessarily those of the NIHR, the Department of Health and Social Care or the UK Health Security Agency. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. No payment was received by any pharmaceutical company or other agency to write this article. The authors were not precluded from accessing data in the study, and accept responsibility to submit for publication. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSalmonella Panama has consistently been reported as a frequently isolated Salmonella serovar in national surveillance datasets, causing both sporadic cases and larger outbreaks. However, this picture has been masked due to most of the focus being placed on the top two serovars associated with nontyphoidal Salmonella (NTS) and invasive NTS disease: Typhimurium and Enteritidis. Previous works on S. Panama have determined transmission to include human faeces and breast milk, as well as non-human sources such as environmental reservoirs and animals (reptiles and pigs used for food). In contrast to most of the Salmonella serovars causing gastroenteritis, S. Panama has also been associated with a range of systemic infections including septicaemia, meningitis, and osteomyelitis, mostly affecting infants. The patterns of antimicrobial resistance of this pathogen were not well known, with studies reporting a mixture of different antimicrobial resistance profiles. Added value of this studyHere we conducted a large-scale study of 836 globally relevant S. Panama isolates to understand global population structure and disease ecology. The S. Panama genomes used in this study were sourced from a combination of historical collections (including the first ever isolated strain of this serovar dating from 1931), national surveillance datasets, and publicly available data. Some of these isolates had been linked to travel, allowing an inferred location for understanding population structure. Overall, this assembled S. Panama collection spanned a range of 88 years and covered 45 countries and regions of all inhabited continents. We applied bacterial phylodynamic approaches to determine population structure, evolutionary history, and clade-specific trends of invasiveness and antimicrobial resistance correlated with geo-temporal parameters. Implications of all the available evidenceThis study revealed the population structure and global ecology of S. Panama, indicating that multidrug resistant S. Panama circulates in European and Asian regions, and presents an increased number of genetic markers for extra-intestinal invasiveness. The transmission and expansion of antimicrobial-resistant S. Panama strains presented in this study highlight the significance of supporting control and monitoring efforts from an international perspective.

genomics↗

bioRxiv2023

Salmonella Infantis, the emerging human multidrug resistant pathogen - a One Health perspective

Salmonella Infantis presents an ever-increasing threat to public health due to its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). Whole genome sequences of 5,284 S. Infantis strains from 74 countries, isolated between 1989 and 2020 from a wide variety of sources including humans, animals, and food, were analysed to compare genetic phylogeny, AMR determinants and plasmid presence. The global S. Infantis population structure diverged into three clusters: a North American cluster, European cluster and a global cluster. The levels of AMR varied between the S. Infantis clusters and by isolation source; 73% of poultry isolates had multidrug resistance (MDR) compared to 35% of human isolates. This correlated with plasmid of emerging S. Infantis (pESI) presence; 71% of poultry isolates contained pESI versus 32% of human isolates. This provides important information for public health teams engaged in reducing the spread of this pathogen.

microbiology↗

bioRxiv2019

A real-time PCR for the differentiation of typhoidal and non-typhoidal Salmonella

Rapid and accurate differentiation of Salmonella spp. causing enteric fever from non-typhoidal Salmonella is essential for clinical management of cases, laboratory risk management and implementation of public health measures. Current methods used for confirmation of identification including biochemistry and serotyping as well as whole genome sequencing analyses, takes several days. Here we report the development and evaluation of a real-time PCR assay that can be performed directly on crude DNA extracts from bacterial colonies, for the rapid identification of typhoidal and non-typhoidal Salmonella. This novel two-hour assay identifies the genus Salmonella by detecting the ttr gene, encoding tetrathionate reductase, and defines typhoidal Salmonella by the detection of S. Typhi and Paratyphi-specific gene combinations. PCR assay performance was determined using 211 clinical cultures of Salmonella (114 non-typhoidal and 97 Typhoidal strains) and 7 clinical non-Salmonella cultures. In addition, the specificity of the assay was evaluated in silico using a diverse in-house collection of 1882 Salmonella whole genome sequences. The real-time PCR results for 218 isolates and the genomic analysis of the 1882 isolates produced 100% sensitivity and 100% specificity (based on a 7 gene profile) for identifying typhoidal Salmonella compared to the Salmonella whole genome sequening identification methods currently used at Public Health England. This paper describes a robust real-time PCR assay for the rapid, accurate identification of typhoidal and non-typhoidal Salmonella which will be invaluable for the urgent screening of isolates from symptomatic individuals, the safe processing of isolates in laboratories and for assisting the management of public health risks.

microbiology↗

bioRxiv2019

Informal genomic surveillance of regional distribution of Salmonella Typhi genotypes and antimicrobial resistance via returning travellers

Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever, a systemic human infection with a burden exceeding 20 million cases each year that occur disproportionately among children in low and middle income countries. Antimicrobial therapy is the mainstay for treatment, but resistance to multiple agents is common. Here we report genotypes and antimicrobial resistance (AMR) determinants detected from routine whole-genome sequencing (WGS) of 533 S. Typhi isolates referred to Public Health England between April 2014 and April 2017, 488 (92%) of which had accompanying patient travel information obtained via an enhanced surveillance questionnaire. The majority of cases involved S. Typhi 4.3.1 (H58) linked with travel to South Asia (58%). Travel to East and West Africa were associated with genotypes 4.3.1 and 3.3.1, respectively. Point mutations in the quinolone resistance determining region (QRDR), associated with reduced susceptibility to fluoroquinolones, were very common (85% of all cases) but the frequency varied significantly by region of travel: 95% in South Asia, 43% in East Africa, 27% in West Africa. QRDR triple mutants, resistant to ciprofloxacin, were restricted to 4.3.1 lineage II and associated with travel to India, accounting for 23% of cases reporting travel to the country. Overall 24% of isolates were MDR, however the frequency varied significantly by region and country of travel: 27% in West Africa, 52% in East Africa, 55% in Pakistan, 24% in Bangladesh, 3% in India. MDR determinants were plasmid-borne (IncHI1 PST2 plasmids) in S. Typhi 3.1.1 linked to West Africa, but in all other regions MDR was chromosomally integrated in 4.3.1 lineage I. We propose that routine WGS data from travel-associated cases in industrialised countries could serve as informal sentinel AMR genomic surveillance data for countries where WGS is not available or routinely performed.\n\nAuthor SummaryOur data demonstrate how routine WGS data produced by Public Health England can be further mined for informal passive surveillance of Salmonella Typhi circulating in different geographical regions where typhoid is endemic. We have shown the public health utility of a simplified approach to WGS reporting based on the GenoTyphi genotyping framework and nomenclature, which doesnt require the generation of a phylogenetic tree or other phylogenetic analysis. These approaches yielded results consistent with previously reported antimicrobial resistance (AMR) patterns of S. Typhi, including prevalence of multi-drug resistant (MDR) and fluoroquinolone resistance in different regions in association with different pathogen variants. These data provide a rationale and framework for the extraction and reporting of geographically stratified genotype and AMR data from public health labs in non-endemic countries. Prospective analysis and reporting of such data could potentially detect shifts in regional S. Typhi populations, such as replacement or spread of different subclades and the emergence and dissemination of MDR, fluoroquinolone resistant and/or extensively drug resistant S. Typhi, providing valuable data to inform typhoid control measures in low and middle income countries that are still building their genomics capacity.

microbiology↗

bioRxiv2018

Evaluation of whole genome sequencing for the identification and typing of Vibrio cholerae

Epidemiological and microbiological data on Vibrio cholerae isolated between 2004 and 2017 (n=836) and held in the Public Health England culture archive were reviewed. The traditional biochemical species identification and serological typing results were compared with the genome derived species identification and serotype for a sub-set of isolates (n=152). Of the 836 isolates, 750 (89.7%) were from faecal specimens, 206 (24.6%) belonged to serogroup O1 and seven (0.8%) were serogroup O139, and 792 (94.7%) isolates from patients reporting recent travel abroad, most commonly to India (n=209) and Pakistan (n=104). Of the 152 isolates of V. cholerae speciated by kmer identification, 149 (98.1%) were concordant with the traditional biochemical approach. Traditional serotyping results were 100% concordant with the whole genome sequencing (WGS) analysis for identification of serogroups O1 and O139 and Classical and El Tor biotypes. ctxA was detected in all isolates of V. cholerae O1 El Tor and O139 belonging to sequence type (ST) 69, and in V. cholerae O1 Classical variants belonging to ST73. A phylogeny of isolates belonging to ST69 from UK travellers clustered geographically, with isolates from India and Pakistan located on separate branches. Moving forward, WGS data from UK travellers will contribute to global surveillance programs, and the monitoring of emerging threats to public health and the global dissemination of pathogenic lineages. At the national level, these WGS data will inform the timely reinforcement of direct public health messaging to travellers and mitigate the impact of imported infections and the associated risks to public health.

microbiology↗