Publications by authors named "Ben Pascoe"

46 Publications

Genome evolution and the emergence of pathogenicity in avian Escherichia coli.

Nat Commun 2021 02 3;12(1):765. Epub 2021 Feb 3.

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK.

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 diverse 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 divergent 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.
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http://dx.doi.org/10.1038/s41467-021-20988-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858641PMC
February 2021

Stress resistance associated with multi-host transmission and enhanced biofilm formation at 42 °C among hyper-aerotolerant generalist Campylobacter jejuni.

Food Microbiol 2021 May 6;95:103706. Epub 2020 Dec 6.

University of Science and Technology, Zewail City of Science and Technology, Giza, Egypt; Department of Bacteriology, Mycology and Immunology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt. Electronic address:

One of the emerging conundrums of Campylobacter food-borne illness is the bacterial ability to survive stressful environmental conditions. We evaluated the heterogeneity among 90 C. jejuni and 21 C. coli isolates from different sources in Egypt with respect to biofilm formation capabilities (under microaerobic and aerobic atmosphere) and resistance to a range of stressors encountered along the food chain (aerobic stress, refrigeration, freeze-thaw, heat, peracetic acid, and osmotic stress). High prevalence (63%) of hyper-aerotolerant (HAT) isolates was observed, exhibiting also a significantly high tolerance to heat, osmotic stress, refrigeration, and freeze-thaw stress, coupled with high biofilm formation ability which was clearly enhanced under aerobic conditions, suggesting a potential link between stress adaptation and biofilm formation. Most HAT multi-stress resistant and strong biofilm producing C. jejuni isolates belonged to host generalist clonal complexes (ST-21, ST-45, ST-48 and ST-206). These findings highlight the potential role of oxidative stress response systems in providing cross-protection (resistance to other multiple stress conditions) and enhancing biofilm formation in Campylobacter and suggest that selective pressures encountered in hostile environments have shaped the epidemiology of C. jejuni in Egypt by selecting the transmission of highly adapted isolates, thus promoting the colonization of multiple host species by important disease-causing lineages.
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http://dx.doi.org/10.1016/j.fm.2020.103706DOI Listing
May 2021

Genome-Wide Identification of Host-Segregating Single-Nucleotide Polymorphisms for Source Attribution of Clinical Campylobacter coli Isolates.

Appl Environ Microbiol 2020 11 24;86(24). Epub 2020 Nov 24.

French National Reference Center for Campylobacters & Helicobacters, Bordeaux Hospital University Center, Bordeaux, France

is among the most common causes of gastroenteritis worldwide. and are the most common species causing human disease. DNA sequence-based methods for strain characterization have focused largely on , responsible for 80 to 90% of infections, meaning that epidemiology has lagged behind. Here, we have analyzed the genome of 450 isolates to determine genetic markers that can discriminate isolates sampled from 3 major reservoir hosts (chickens, cattle, and pigs). These markers then were applied to identify the source of infection of 147 strains from French clinical cases. Using STRUCTURE software, 259 potential host-segregating markers were revealed by probabilistic characterization of single-nucleotide polymorphism (SNP) frequency variation in strain collections from three different hosts. These SNPs were found in 41 genes or intergenic regions, mostly coding for proteins involved in motility and membrane functions. Source attribution of clinical isolates based on the differential presence of these markers confirmed chickens as the most common source of infection in France. Genome-wide and source attribution studies based on species have shown their importance for the understanding of foodborne infections. Although the use of multilocus sequence typing based on 7 genes from is a powerful method to structure populations, when applied to , results have not clearly demonstrated its robustness. Therefore, we aim to provide more accurate data based on the identification of single-nucleotide polymorphisms. Results from this study reveal an important number of host-segregating SNPs, found in proteins involved in motility, membrane functions, or DNA repair systems. These findings offer new, interesting opportunities for further study of adaptation to its environment. Additionally, the results demonstrate that poultry is potentially the main reservoir of in France.
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http://dx.doi.org/10.1128/AEM.01787-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688228PMC
November 2020

A 500-year tale of co-evolution, adaptation, and virulence: Helicobacter pylori in the Americas.

ISME J 2021 Jan 2;15(1):78-92. Epub 2020 Sep 2.

Unidad de Investigacion en Enfermedades Infecciosas, UMAE Pediatria, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico.

Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region.
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http://dx.doi.org/10.1038/s41396-020-00758-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853065PMC
January 2021

Genomic epidemiology of Campylobacter jejuni associated with asymptomatic pediatric infection in the Peruvian Amazon.

PLoS Negl Trop Dis 2020 08 10;14(8):e0008533. Epub 2020 Aug 10.

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.

Campylobacter 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 likely 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 divergent strains suggesting an important role for host factors in the cryptic epidemiology of campylobacteriosis in LMICs.
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http://dx.doi.org/10.1371/journal.pntd.0008533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440661PMC
August 2020

Agricultural intensification and the evolution of host specialism in the enteric pathogen .

Proc Natl Acad Sci U S A 2020 05 4;117(20):11018-11028. Epub 2020 May 4.

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, BA2 7AY Bath, United Kingdom;

Modern agriculture has dramatically changed the distribution of animal species on Earth. Changes to host ecology have a major impact on the microbiota, potentially increasing the risk of zoonotic pathogens being transmitted to humans, but the impact of intensive livestock production on host-associated bacteria has rarely been studied. Here, we use large isolate collections and comparative genomics techniques, linked to phenotype studies, to understand the timescale and genomic adaptations associated with the proliferation of the most common food-born bacterial pathogen () in the most prolific agricultural mammal (cattle). Our findings reveal the emergence of cattle specialist lineages from a background of host generalist strains that coincided with the dramatic rise in cattle numbers in the 20th century. Cattle adaptation was associated with horizontal gene transfer and significant gene gain and loss. This may be related to differences in host diet, anatomy, and physiology, leading to the proliferation of globally disseminated cattle specialists of major public health importance. This work highlights how genomic plasticity can allow important zoonotic pathogens to exploit altered niches in the face of anthropogenic change and provides information for mitigating some of the risks posed by modern agricultural systems.
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http://dx.doi.org/10.1073/pnas.1917168117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245135PMC
May 2020

The emergence of plasmid-borne cfr-mediated linezolid resistant-staphylococci in Vietnam.

J Glob Antimicrob Resist 2020 09 27;22:462-465. Epub 2020 Apr 27.

Biotechnology Center of Ho Chi Minh City, Viet Nam.

Objectives: Linezolid is one of the last resort antibiotics effectively used in the treatment of infections caused by multidrug-resistant Gram-positive bacteria. Recent outbreaks of Linezolid resistance have been the great concern worldwide, while many countries have not experienced it. In this work, we aimed to evaluate the existence of linezolid resistance and further clarify potential resistance mechanism(s) in staphylococcal isolates obtained from the hospital in Vietnam, a country in which linezolid resistance had not been previously detected.

Methods: Seventy staphylococcal clinical isolates including MRSA (n=63) and methicillin-resistant coagulase-negative staphylococci (MRCNS, n=7) were collected and analyzed for linezolid resistance. Linezolid-resistant isolates were submitted for whole genome sequencing to search for the resistance determinants.

Results: We identified two coagulase-negative staphylococcal isolates that were resistant to linezolid. Whole genome sequencing revealed several alterations in the 23S rRNA and L3, L17, L22, L24, L30 ribosomal proteins. Importantly, both isolates harbour the chloramphenicol/florfenicol resistance (cfr) gene on a plasmid. The plasmid was closely identical to the pLRSA417 plasmid that was originally reported in China.

Conclusions: To the best of our knowledge, this is the first report of cfr-mediated linezolid resistance in clinically isolated staphylococci in Vietnam. We suggest that adequate surveillance is necessary to monitor the dissemination of linezolid resistance among staphylococcal species and other important pathogens.
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http://dx.doi.org/10.1016/j.jgar.2020.04.008DOI Listing
September 2020

Genetic Diversity of Composite Enterotoxigenic Staphylococcus epidermidis Pathogenicity Islands.

Genome Biol Evol 2019 12;11(12):3498-3509

Department of Food Hygiene and Consumer Health Protection, Wrocław University of Environmental and Life Sciences, Poland.

The only known elements encoding enterotoxins in coagulase-negative staphylococci are composite Staphylococcus epidermidis pathogenicity islands (SePIs), including SePI and S. epidermidis composite insertion (SeCI) regions. We investigated 1545 Staphylococcus spp. genomes using whole-genome MLST, and queried them for genes of staphylococcal enterotoxin family and for 29 ORFs identified in prototype SePI from S. epidermidis FRI909. Enterotoxin-encoding genes were identified in 97% of Staphylococcus aureus genomes, in one Staphylococcus argenteus genome and in nine S. epidermidis genomes. All enterotoxigenic S. epidermidis strains carried composite SePI, encoding sec and sel enterotoxin genes, and were assigned to a discrete wgMLST cluster also containing genomes with incomplete islands located in the same region as complete SePI in enterotoxigenic strains. Staphylococcus epidermidis strains without SeCI and SePI genes, and strains with complete SeCI and no SePI genes were identified but no strains were found to carry only SePI and not SeCI genes. The systematic differences between SePI and SeCI regions imply a lineage-specific pattern of inheritance and support independent acquisition of the two elements in S. epidermidis. We provided evidence of reticulate evolution of mobile elements that contain elements with different putative ancestry, including composite SePI that contains genes found in other coagulase-negative staphylococci (SeCI), as well as in S. aureus (SePI-like elements). We conclude that SePI-associated elements present in nonenterotoxigenic S. epidermidis represent a scaffold associated with acquisition of virulence-associated genes. Gene exchange between S. aureus and S. epidermidis may promote emergence of new pathogenic S. epidermidis clones.
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http://dx.doi.org/10.1093/gbe/evz259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931896PMC
December 2019

Gene pool transmission of multidrug resistance among Campylobacter from livestock, sewage and human disease.

Environ Microbiol 2019 12 27;21(12):4597-4613. Epub 2019 Aug 27.

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, BA27AY, Bath, UK.

The use of antimicrobials in human and veterinary medicine has coincided with a rise in antimicrobial resistance (AMR) in the food-borne pathogens Campylobacter jejuni and Campylobacter coli. Faecal contamination from the main reservoir hosts (livestock, especially poultry) is the principal route of human infection but little is known about the spread of AMR among source and sink populations. In particular, questions remain about how Campylobacter resistomes interact between species and hosts, and the potential role of sewage as a conduit for the spread of AMR. Here, we investigate the genomic variation associated with AMR in 168 C. jejuni and 92 C. coli strains isolated from humans, livestock and urban effluents in Spain. AMR was tested in vitro and isolate genomes were sequenced and screened for putative AMR genes and alleles. Genes associated with resistance to multiple drug classes were observed in both species and were commonly present in multidrug-resistant genomic islands (GIs), often located on plasmids or mobile elements. In many cases, these loci had alleles that were shared among C. jejuni and C. coli consistent with horizontal transfer. Our results suggest that specific antibiotic resistance genes have spread among Campylobacter isolated from humans, animals and the environment.
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http://dx.doi.org/10.1111/1462-2920.14760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916351PMC
December 2019

Domestication of Campylobacter jejuni NCTC 11168.

Microb Genom 2019 07 16;5(7). Epub 2019 Jul 16.

Swansea University Medical School, Swansea University, Singleton Park, Swansea, UK.

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. Campylobacter 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 Campylobacter 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 ampicillin. 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.
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http://dx.doi.org/10.1099/mgen.0.000279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700657PMC
July 2019

Core genome sequence analysis to characterize Salmonella enterica serovar Rissen ST469 from a swine production chain.

Int J Food Microbiol 2019 Sep 28;304:68-74. Epub 2019 May 28.

Integrative Research Center for Veterinary Preventive Medicine, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand. Electronic address:

Salmonella enterica subsp. enterica serotype Rissen is the predominant serotype found in Thai pork production and can be transmitted to humans through contamination of the food chain. This study was conducted to investigate the genetic relationships between serovar Rissen isolates from all levels of the pork production chain and evaluate the ability of the in silico antimicrobial resistance (AMR) genotypes to predict the phenotype of serovar Rissen. A total of 38 serovar Rissen isolates were tested against eight antibiotic agents by a disk diffusion method and the whole genomes of all isolates were sequenced to detect AMR genetic elements using the ResFinder database.A total of 86.84% of the isolates were resistant to tetracycline, followed by ampicillin (78.96%) and sulfonamide-trimethoprim (71.05%). Resistance to more than one antimicrobial agent was observed in 78.95% of the isolates, with the most common pattern showing resistance to ampicillin, chloramphenicol, streptomycin, sulfonamide-trimethoprim, and tetracycline. The results of genotypic AMR indicated that 89.47% of the isolates carried tet(A), 84.22% carried bla, 78.95% carried sul3, and 78.95% carried dfrA12. The genotypic prediction of phenotypic resistance resulted in a mean sensitivity of 97.45% and specificity of 75.48%. Analysis by core genome multilocus sequence typing (cgMLST) demonstrated that the Salmonella isolates from various sources and different locations shared many of the same core genome loci. This implies that serovar Rissen has infected every stage of the pork production process and that contamination can occur in every part of the production chain.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2019.05.022DOI Listing
September 2019

Prevalence of faecal carriage of extended-spectrum β-lactamase (ESBL)-producing in veterinary hospital staff and students.

Vet Rec Open 2019 7;6(1):e000307. Epub 2019 Jan 7.

Department of Epidemiology and Population Health, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.

Extended-spectrum β-lactamase (ESBL)-producing bacteria causing clinical infections are often also multidrug-resistant (MDR; resistance to ≥3 antimicrobial drug classes), therefore treatment options may be limited. High carriage rates of these potentially zoonotic bacteria have been found in livestock and companion animals. Therefore, people working in veterinary hospitals may be a high-risk population for carriage. This is the first study to determine the prevalence and longitudinal carriage of antimicrobial-resistant (AMR) and ESBL-producing faecal in veterinary hospital staff and students. Prevalence of faecal AMR and ESBL-producing was determined in 84 staff members and students in three UK veterinary hospitals. Twenty-seven participants were followed for six weeks to investigate longitudinal carriage. Antimicrobial susceptibility and phenotypic ESBL production were determined and selected isolates were whole genome sequenced. ESBL-producing were isolated from five participants (5.95 per cent; 95 per cent CI 0.89 to 11.0 per cent); two participants carried ESBL-producing resistant to all antimicrobials tested. Carriage of MDR was common (32.1 per cent; 95per cent CI 22.2 to 42.1 per cent) and there was a high prevalence of ciprofloxacin resistance (11.9 per cent; 95 per cent CI 4.98 to 18.8 per cent). ESBL-producing were isolated from seven longitudinal participants (25.9 per cent; 95 per cent CI 9.40 to 42.5 per cent); two participants carried ESBL-producing for the entire study period. Twenty-six participants (96.3 per cent; 95 per cent CI 89.2 to 100) carried ≥1 MDR isolate during the six-week period, with seven participants (25.9 per cent) carrying ≥1 MDR isolate for at least five out of six weeks. The prevalence of faecal ESBL-producing in cross-sectional participants is similar to asymptomatic general populations. However, much higher levels of carriage were observed longitudinally in participants. It is vital that veterinary hospitals implement gold-standard biosecurity to prevent transmission of MDR and ESBL-producing bacteria between patients and staff. Healthcare providers should be made aware that people working in veterinary hospitals are a high-risk population for carriage of MDR and ESBL-producing bacteria, and that this poses a risk to the carrier and for transmission of resistance throughout the wider community.
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http://dx.doi.org/10.1136/vetreco-2018-000307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327872PMC
January 2019

Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis.

Nat Commun 2018 11 28;9(1):5034. Epub 2018 Nov 28.

The Milner Centre for Evolution, University of Bath, Claverton Down, Bath, BA2 7AY, UK.

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 divergent 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.
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http://dx.doi.org/10.1038/s41467-018-07368-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261936PMC
November 2018

Genomic epidemiology of clinical Campylobacter spp. at a single health trust site.

Microb Genom 2018 10 11;4(10). Epub 2018 Oct 11.

5​University of Wolverhampton, Wolverhampton, UK.

Campylobacter is the leading cause of bacterial enteritis in the developed world, and infections with the organism are largely sporadic in nature. Links between sporadic cases have not been established, with the majority of infections thought to be caused by genetically distinct isolates. Using a read-mapping approach, 158 clinical isolates collected during 2014 from the greater Nottinghamshire area were analysed to assess the local population structure and investigate potential case linkages between sporadic cases of campylobacteriosis. Four instances (2.5 %) of case linkage were observed across the dataset. This study demonstrates that case linkage does occur between sporadic Campylobacter infections, and provides evidence that a dual multi-locus sequence typing/within-lineage single nucleotide polymorphism typing approach to Campylobacter genomic epidemiology provides a benefit to public-health investigations.
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http://dx.doi.org/10.1099/mgen.0.000227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249439PMC
October 2018

A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk.

BMC Biol 2018 08 2;16(1):84. Epub 2018 Aug 2.

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, UK.

Background: Helicobacter pylori are stomach-dwelling bacteria that are present in about 50% of the global population. Infection is asymptomatic in most cases, but it has been associated with gastritis, gastric ulcers and gastric cancer. Epidemiological evidence shows that progression to cancer depends upon the host and pathogen factors, but questions remain about why cancer phenotypes develop in a minority of infected people. Here, we use comparative genomics approaches to understand how genetic variation amongst bacterial strains influences disease progression.

Results: We performed a genome-wide association study (GWAS) on 173 H. pylori isolates from the European population (hpEurope) with known disease aetiology, including 49 from individuals with gastric cancer. We identified SNPs and genes that differed in frequency between isolates from patients with gastric cancer and those with gastritis. The gastric cancer phenotype was associated with the presence of babA and genes in the cag pathogenicity island, one of the major virulence determinants of H. pylori, as well as non-synonymous variations in several less well-studied genes. We devised a simple risk score based on the risk level of associated elements present, which has the potential to identify strains that are likely to cause cancer but will require refinement and validation.

Conclusion: There are a number of challenges to applying GWAS to bacterial infections, including the difficulty of obtaining matched controls, multiple strain colonization and the possibility that causative strains may not be present when disease is detected. Our results demonstrate that bacterial factors have a sufficiently strong influence on disease progression that even a small-scale GWAS can identify them. Therefore, H. pylori GWAS can elucidate mechanistic pathways to disease and guide clinical treatment options, including for asymptomatic carriers.
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http://dx.doi.org/10.1186/s12915-018-0550-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090961PMC
August 2018

Genomic epidemiology of the commercially important pathogen Renibacterium salmoninarum within the Chilean salmon industry.

Microb Genom 2018 09 24;4(9). Epub 2018 Jul 24.

1​Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, UK.

Renibacterium salmoninarum is the causative agent of bacterial kidney disease (BKD), which is a commercially important disease of farmed salmonids. Typing by conventional methods provides limited information on the evolution and spread of this pathogen, as there is a low level of standing variation within the R. salmoninarum population. Here, we apply whole-genome sequencing to 42 R. salmoninarum isolates from Chile, primarily from salmon farms, in order to understand the epidemiology of BKD in this country. The patterns of genomic variation are consistent with multiple introductions to Chile, followed by rapid dissemination over a 30 year period. The estimated dates of introduction broadly coincide with major events in the development of the Chilean aquaculture industry. We find evidence for significant barriers to transmission of BKD in the Chilean salmon production chain that may also be explained by previously undescribed signals of host tropism in R. salmoninarum. Understanding the genomic epidemiology of BKD can inform disease intervention and improve sustainability of the economically important salmon industry. This article contains data hosted by Microreact.
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http://dx.doi.org/10.1099/mgen.0.000201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202448PMC
September 2018

Epistasis analysis uncovers hidden antibiotic resistance-associated fitness costs hampering the evolution of MRSA.

Genome Biol 2018 07 18;19(1):94. Epub 2018 Jul 18.

School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.

Background: Fitness costs imposed on bacteria by antibiotic resistance mechanisms are believed to hamper their dissemination. The scale of these costs is highly variable. Some, including resistance of Staphylococcus aureus to the clinically important antibiotic mupirocin, have been reported as being cost-free, which suggests that there are few barriers preventing their global spread. However, this is not supported by surveillance data in healthy communities, which indicate that this resistance mechanism is relatively unsuccessful.

Results: Epistasis analysis on two collections of MRSA provides an explanation for this discord, where the mupirocin resistance-conferring mutation of the ileS gene appears to affect the levels of toxins produced by S. aureus when combined with specific polymorphisms at other loci. Proteomic analysis demonstrates that the activity of the secretory apparatus of the PSM family of toxins is affected by mupirocin resistance. As an energetically costly activity, this reduction in toxicity masks the fitness costs associated with this resistance mutation, a cost that becomes apparent when toxin production becomes necessary. This hidden fitness cost provides a likely explanation for why this mupirocin-resistance mechanism is not more prevalent, given the widespread use of this antibiotic.

Conclusions: With dwindling pools of antibiotics available for use, information on the fitness consequences of the acquisition of resistance may need to be considered when designing antibiotic prescribing policies. However, this study suggests there are levels of depth that we do not understand, and that holistic, surveillance and functional genomics approaches are required to gain this crucial information.
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http://dx.doi.org/10.1186/s13059-018-1469-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052701PMC
July 2018

The Potential of Isolation Source to Predict Colonization in Avian Hosts: A Case Study in Strains From Three Bird Species.

Front Microbiol 2018 29;9:591. Epub 2018 Mar 29.

Department of Medical Sciences, Zoonosis Science Center, Uppsala University, Uppsala, Sweden.

is the primary cause of bacterial gastroenteritis worldwide, infecting humans mostly through consumption of contaminated poultry. is common in the gut of wild birds, and shows distinct strain-specific association to particular bird species. This contrasts with farm animals, in which several genotypes co-exist. It is unclear if the barriers restricting transmission between host species of such specialist strains are related to environmental factors such as contact between host species, bacterial survival in the environment, etc., or rather to strain specific adaptation to the intestinal environment of specific hosts. We compared colonization dynamics between two host-specific from a song thrush (ST-1304 complex) and a mallard (ST-995), and a generalist strain from chicken (ST-21 complex) in a wild host, the mallard (. In 18-days infection experiments, the song thrush strain showed only weak colonization and was cleared from all birds after 10 days, whereas both mallard and chicken strains remained stable. When the chicken strain was given 4 days prior to co-infection of the same birds with a mallard strain, it was rapidly outcompeted by the latter. In contrast, when the mallard strain was given 4 days prior to co-infection with the chicken strain, the mallard strain remained and expansion of the chicken strain was delayed. Our results suggest strain-specific differences in the ability of to colonize mallards, likely associated with host origin. This difference might explain observed host association patterns in from wild birds.
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http://dx.doi.org/10.3389/fmicb.2018.00591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884941PMC
March 2018

Lineage-specific plasmid acquisition and the evolution of specialized pathogens in Bacillus thuringiensis and the Bacillus cereus group.

Mol Ecol 2018 04 2;27(7):1524-1540. Epub 2018 Apr 2.

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, UK.

Bacterial plasmids can vary from small selfish genetic elements to large autonomous replicons that constitute a significant proportion of total cellular DNA. By conferring novel function to the cell, plasmids may facilitate evolution but their mobility may be opposed by co-evolutionary relationships with chromosomes or encouraged via the infectious sharing of genes encoding public goods. Here, we explore these hypotheses through large-scale examination of the association between plasmids and chromosomal DNA in the phenotypically diverse Bacillus cereus group. This complex group is rich in plasmids, many of which encode essential virulence factors (Cry toxins) that are known public goods. We characterized population genomic structure, gene content and plasmid distribution to investigate the role of mobile elements in diversification. We analysed coding sequence within the core and accessory genome of 190 B. cereus group isolates, including 23 novel sequences and genes from 410 reference plasmid genomes. While cry genes were widely distributed, those with invertebrate toxicity were predominantly associated with one sequence cluster (clade 2) and phenotypically defined Bacillus thuringiensis. Cry toxin plasmids in clade 2 showed evidence of recent horizontal transfer and variable gene content, a pattern of plasmid segregation consistent with transfer during infectious cooperation. Nevertheless, comparison between clades suggests that co-evolutionary interactions may drive association between plasmids and chromosomes and limit wider transfer of key virulence traits. Proliferation of successful plasmid and chromosome combinations is a feature of specialized pathogens with characteristic niches (Bacillus anthracis, B. thuringiensis) and has occurred multiple times in the B. cereus group.
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http://dx.doi.org/10.1111/mec.14546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947300PMC
April 2018

Convergent Amino Acid Signatures in Polyphyletic Campylobacter jejuni Subpopulations Suggest Human Niche Tropism.

Genome Biol Evol 2018 03;10(3):763-774

Department of Biology and Biochemistry, The Milner Centre for Evolution, University of Bath, United Kingdom.

Human infection with the gastrointestinal pathogen Campylobacter jejuni is dependent upon the opportunity for zoonotic transmission and the ability of strains to colonize the human host. Certain lineages of this diverse organism are more common in human infection but the factors underlying this overrepresentation are not fully understood. We analyzed 601 isolate genomes from agricultural animals and human clinical cases, including isolates from the multihost (ecological generalist) ST-21 and ST-45 clonal complexes (CCs). Combined nucleotide and amino acid sequence analysis identified 12 human-only amino acid KPAX clusters among polyphyletic lineages within the common disease causing CC21 group isolates, with no such clusters among CC45 isolates. Isolate sequence types within human-only CC21 group KPAX clusters have been sampled from other hosts, including poultry, so rather than representing unsampled reservoir hosts, the increase in relative frequency in human infection potentially reflects a genetic bottleneck at the point of human infection. Consistent with this, sequence enrichment analysis identified nucleotide variation in genes with putative functions related to human colonization and pathogenesis, in human-only clusters. Furthermore, the tight clustering and polyphyly of human-only lineage clusters within a single CC suggest the repeated evolution of human association through acquisition of genetic elements within this complex. Taken together, combined nucleotide and amino acid analysis of large isolate collections may provide clues about human niche tropism and the nature of the forces that promote the emergence of clinically important C. jejuni lineages.
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http://dx.doi.org/10.1093/gbe/evy026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841378PMC
March 2018

Comparative genomic survey of Bacillus cereus sensu stricto isolates from the dairy production chain in Brazil.

FEMS Microbiol Lett 2018 02;365(3)

Departamento de Medicina Veterinária, Avenida Duque de Caxias Norte 225, Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos (FZEA), CEP 13635-900 Pirassununga, São Paulo, Brazil.

The genomes of 262 Bacillus cereus isolates were analyzed including 69 isolates sampled from equipment, raw milk and dairy products from Brazil. The population structure of isolates showed strains belonging to known phylogenetic groups II, III, IV, V and VI. Almost all the isolates obtained from dairy products belonged to group III. Investigation of specific alleles revealed high numbers of isolates carrying toxin-associated genes including cytK (53.62%), hblA (59.42%), hblC (44.93%), hblD (53.62%), nheA (84.06%), nheB (89.86%) and nheC (84.06%) with isolates belonging to groups IV and V having significant higher prevalence of hblACD and group IV of CytK genes. Strains from dairy products had significantly lower prevalence of CytK and hblACD genes compared to isolates from equipment and raw milk/bulk tanks. Genes related to sucrose metabolism were detected at higher frequency in isolates obtained from raw milk compared to strains from equipment and utensils. The population genomic analysis demonstrated the diversity of strains and variability of putative function among B. cereus group isolates in Brazilian dairy production, with large numbers of strains potentially able to cause foodborne illness. This detailed information will contribute to targeted interventions to reduce milk contamination and spoilage associated with B. cereus in Brazil.
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http://dx.doi.org/10.1093/femsle/fnx283DOI Listing
February 2018

Molecular epidemiology and comparative genomics of Campylobacter concisus strains from saliva, faeces and gut mucosal biopsies in inflammatory bowel disease.

Sci Rep 2018 01 30;8(1):1902. Epub 2018 Jan 30.

Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.

Campylobacter concisus is an emerging pathogen associated with inflammatory bowel disease (IBD), yet little is known about the genetic diversity of C. concisus in relation to host niches and disease. We isolated 104 C. concisus isolates from saliva, mucosal biopsies and faecal samples from 41 individuals (26 IBD, 3 Gastroenteritis (GE), 12 Healthy controls (HC)). Whole genomes were sequenced and the dataset pan-genome examined, and genomic information was used for typing using multi-locus-sequence typing (MLST). C. concisus isolates clustered into two main groups/genomospecies (GS) with 71 distinct sequence types (STs) represented. Sampling site (p < 0.001), rather than disease phenotype (p = 1.00) was associated with particular GS. We identified 97 candidate genes associated with increase or decrease in prevalence during the anatomical descent from the oral cavity to mucosal biopsies to faeces. Genes related to cell wall/membrane biogenesis were more common in oral isolates, whereas genes involved in cell transport, metabolism and secretory pathways were more prevalent in enteric isolates. Furthermore, there was no correlation between individual genetic diversity and clinical phenotype. This study confirms the genetic heterogeneity of C. concisus and provides evidence that genomic variation is related to the source of isolation, but not clinical phenotype.
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http://dx.doi.org/10.1038/s41598-018-20135-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790007PMC
January 2018

Genome Comparison of Erythromycin Resistant from Turkeys Identifies Hosts and Pathways for Horizontal Spread of (B) Genes.

Front Microbiol 2017 15;8:2240. Epub 2017 Nov 15.

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.

Pathogens in the genus are the most common cause of food-borne bacterial gastro-enteritis. Campylobacteriosis, caused principally by and , is transmitted to humans by food of animal origin, especially poultry. As for many pathogens, antimicrobial resistance in is increasing at an alarming rate. Erythromycin prescription is the treatment of choice for clinical cases requiring antimicrobial therapy but this is compromised by mobility of the erythromycin resistance gene (B) between strains. Here, we evaluate resistance to six antimicrobials in 170 isolates (133 and 37 ) from turkeys. Erythromycin resistant isolates ( = 85; 81 and 4 ) were screened for the presence of the (B) gene, that has not previously been identified in isolates from turkeys. The genomes of two positive isolates were sequenced and in both isolates the (B) gene clustered with resistance determinants against aminoglycosides plus tetracycline, including , and (O) genes. Comparative genomic analysis identified identical (B) sequences among from turkeys, from pigs and and from humans. This is consistent with multiple horizontal transfer events among different bacterial species colonizing turkeys. This example highlights the potential for dissemination of antimicrobial resistance across bacterial species boundaries which may compromise their effectiveness in antimicrobial therapy.
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http://dx.doi.org/10.3389/fmicb.2017.02240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695097PMC
November 2017

Comparative Genomics Study of Staphylococcus epidermidis Isolates from Orthopedic-Device-Related Infections Correlated with Patient Outcome.

J Clin Microbiol 2017 10 9;55(10):3089-3103. Epub 2017 Aug 9.

AO Research Institute Davos, Davos, Switzerland

has emerged as an important opportunistic pathogen causing orthopedic-device-related infections (ODRI). This study investigated the association of genome variation and phenotypic features of the infecting isolate with the clinical outcome for the infected patient. isolates were collected from 104 patients with ODRI. Their clinical outcomes were evaluated, after an average of 26 months, as either "cured" or "not cured." The isolates were tested for antibiotic susceptibility and biofilm formation. Whole-genome sequencing was performed on all isolates, and genomic variation was related to features associated with "cured" and "not cured." Strong biofilm formation and aminoglycoside resistance were associated with a "not-cured" outcome ( = 0.031 and < 0.001, respectively). Based on gene-by-gene analysis, some accessory genes were more prevalent in isolates from the "not-cured" group. These included the biofilm-associated gene, the antiseptic resistance gene, the cassette chromosome recombinase-encoding genes and , and the IS-like transposase gene. This study identifies biofilm formation and antibiotic resistance as associated with poor outcome in ODRI. Whole-genome sequencing identified specific genes associated with a "not-cured" outcome that should be validated in future studies. (The study has been registered at ClinicalTrials.gov with identifier NCT02640937.).
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http://dx.doi.org/10.1128/JCM.00881-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625394PMC
October 2017

Local genes for local bacteria: Evidence of allopatry in the genomes of transatlantic Campylobacter populations.

Mol Ecol 2017 Sep 19;26(17):4497-4508. Epub 2017 Jun 19.

The Milner Centre for Evolution, Department of Biology and Biochemistry, Bath University, Claverton Down, Bath, UK.

The genetic structure of bacterial populations can be related to geographical locations of isolation. In some species, there is a strong correlation between geographical distance and genetic distance, which can be caused by different evolutionary mechanisms. Patterns of ancient admixture in Helicobacter pylori can be reconstructed in concordance with past human migration, whereas in Mycobacterium tuberculosis it is the lack of recombination that causes allopatric clusters. In Campylobacter, analyses of genomic data and molecular typing have been successful in determining the reservoir host species, but not geographical origin. We investigated biogeographical variation in highly recombining genes to determine the extent of clustering between genomes from geographically distinct Campylobacter populations. Whole-genome sequences from 294 Campylobacter isolates from North America and the UK were analysed. Isolates from within the same country shared more recently recombined DNA than isolates from different countries. Using 15 UK/American closely matched pairs of isolates that shared ancestors, we identify regions that have frequently and recently recombined to test their correlation with geographical origin. The seven genes that demonstrated the greatest clustering by geography were used in an attribution model to infer geographical origin which was tested using a further 383 UK clinical isolates to detect signatures of recent foreign travel. Patient records indicated that in 46 cases, travel abroad had occurred <2 weeks prior to sampling, and genomic analysis identified that 34 (74%) of these isolates were of a non-UK origin. Identification of biogeographical markers in Campylobacter genomes will contribute to improved source attribution of clinical Campylobacter infection and inform intervention strategies to reduce campylobacteriosis.
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http://dx.doi.org/10.1111/mec.14176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600125PMC
September 2017

Bayesian identification of bacterial strains from sequencing data.

Microb Genom 2016 08 25;2(8):e000075. Epub 2016 Aug 25.

1​Helsinki Institute for Information Technology, Department of Computer Science, University of Helsinki, Helsinki, Finland.

Rapidly assaying the diversity of a bacterial species present in a sample obtained from a hospital patient or an environmental 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 pipeline 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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http://dx.doi.org/10.1099/mgen.0.000075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320594PMC
August 2016

Recombination-Mediated Host Adaptation by Avian Staphylococcus aureus.

Genome Biol Evol 2017 04;9(4):830-842

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, United Kingdom.

Staphylococcus aureus are globally disseminated among farmed chickens causing skeletal muscle infections, dermatitis, and septicaemia. The emergence of poultry-associated lineages has involved zoonotic transmission from humans to chickens but questions remain about the specific adaptations that promote proliferation of chicken pathogens. We characterized genetic variation in a population of genome-sequenced S. aureus isolates of poultry and human origin. Genealogical analysis identified a dominant poultry-associated sequence cluster within the CC5 clonal complex. Poultry and human CC5 isolates were significantly distinct from each other and more recombination events were detected in the poultry isolates. We identified 44 recombination events in 33 genes along the branch extending to the poultry-specific CC5 cluster, and 47 genes were found more often in CC5 poultry isolates compared with those from humans. Many of these gene sequences were common in chicken isolates from other clonal complexes suggesting horizontal gene transfer among poultry associated lineages. Consistent with functional predictions for putative poultry-associated genes, poultry isolates showed enhanced growth at 42 °C and greater erythrocyte lysis on chicken blood agar in comparison with human isolates. By combining phenotype information with evolutionary analyses of staphylococcal genomes, we provide evidence of adaptation, following a human-to-poultry host transition. This has important implications for the emergence and dissemination of new pathogenic clones associated with modern agriculture.
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http://dx.doi.org/10.1093/gbe/evx037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469444PMC
April 2017

Genomic structure and insertion sites of Helicobacter pylori prophages from various geographical origins.

Sci Rep 2017 02 16;7:42471. Epub 2017 Feb 16.

Université de Bordeaux, Centre National de Référence des Campylobacters et Hélicobacters, Bordeaux, France.

Helicobacter pylori genetic diversity is known to be influenced by mobile genomic elements. Here we focused on prophages, the least characterized mobile elements of H. pylori. We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found in H. pylori isolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The genome sizes of these prophages range from 22.6-33.0 Kbp, consisting of 27-39 open reading frames. A 36.6% GC was found in prophages in contrast to 39% in H. pylori genome. Remarkably a conserved integration site was found in over 50% of the cases. Nearly 40% of the prophages harbored insertion sequences (IS) previously described in H. pylori. Tandem repeats were frequently found in the intergenic region between the prophage at the 3' end and the bacterial gene. Furthermore, prophage genomes present a robust phylogeographic pattern, revealing four distinct clusters: one African, one Asian and two European prophage populations. Evidence of recombination was detected within the genome of some prophages, resulting in genome mosaics composed by different populations, which may yield additional H. pylori phenotypes.
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http://dx.doi.org/10.1038/srep42471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311958PMC
February 2017

Genome-Wide Identification of Host-Segregating Epidemiological Markers for Source Attribution in Campylobacter jejuni.

Appl Environ Microbiol 2017 Apr 17;83(7). Epub 2017 Mar 17.

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom

is among the most common worldwide causes of bacterial gastroenteritis. This organism is part of the commensal microbiota of numerous host species, including livestock, and these animals constitute potential sources of human infection. Molecular typing approaches, especially multilocus sequence typing (MLST), have been used to attribute the source of human campylobacteriosis by quantifying the relative abundance of alleles at seven MLST loci among isolates from animal reservoirs and human infection, implicating chicken as a major infection source. The increasing availability of bacterial genomes provides data on allelic variation at loci across the genome, providing the potential to improve the discriminatory power of data for source attribution. Here we present a source attribution approach based on the identification of novel epidemiological markers among a reference pan-genome list of 1,810 genes identified by gene-by-gene comparison of 884 genomes of isolates from animal reservoirs, the environment, and clinical cases. Fifteen loci involved in metabolic activities, protein modification, signal transduction, and stress response or coding for hypothetical proteins were selected as host-segregating markers and used to attribute the source of 42 French and 281 United Kingdom clinical isolates. Consistent with previous studies of British campylobacteriosis, analyses performed using STRUCTURE software attributed 56.8% of British clinical cases to chicken, emphasizing the importance of this host reservoir as an infection source in the United Kingdom. However, among French clinical isolates, approximately equal proportions of isolates were attributed to chicken and ruminant reservoirs, suggesting possible differences in the relative importance of animal host reservoirs and indicating a benefit for further national-scale attribution modeling to account for differences in production, behavior, and food consumption. Accurately quantifying the relative contribution of different host reservoirs to human infection is an ongoing challenge. This study, based on the development of a novel source attribution approach, provides the first results of source attribution in in France. A systematic analysis using gene-by-gene comparison of 884 genomes of isolates, with a pan-genome list of genes, identified 15 novel epidemiological markers for source attribution. The different proportions of French and United Kingdom clinical isolates attributed to each host reservoir illustrate a potential role for local/national variations in transmission dynamics.
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http://dx.doi.org/10.1128/AEM.03085-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359498PMC
April 2017

Genome-wide association of functional traits linked with Campylobacter jejuni survival from farm to fork.

Environ Microbiol 2017 Jan;19(1):361-380

The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, UK.

Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, primarily associated with the consumption of contaminated poultry. C. jejuni lineages vary in host range and prevalence in human infection, suggesting differences in survival throughout the poultry processing chain. From 7343 MLST-characterised isolates, we sequenced 600 C. jejuni and C. coli isolates from various stages of poultry processing and clinical cases. A genome-wide association study (GWAS) in C. jejuni ST-21 and ST-45 complexes identified genetic elements over-represented in clinical isolates that increased in frequency throughout the poultry processing chain. Disease-associated SNPs were distinct in these complexes, sometimes organised in haplotype blocks. The function of genes containing associated elements was investigated, demonstrating roles for cj1377c in formate metabolism, nuoK in aerobic survival and oxidative respiration, and cj1368-70 in nucleotide salvage. This work demonstrates the utility of GWAS for investigating transmission in natural zoonotic pathogen populations and provides evidence that major C. jejuni lineages have distinct genotypes associated with survival, within the host specific niche, from farm to fork.
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http://dx.doi.org/10.1111/1462-2920.13628DOI Listing
January 2017