title: Genome-Wide Identification of Host-Segregating Epidemiological Markers for Source Attribution in Campylobacter jejuni.
abstract: Campylobacteris 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 ofCampylobacter jejuniisolates 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 clinicalC. jejuniisolates. 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.IMPORTANCEAccurately quantifying the relative contribution of different host reservoirs to humanCampylobacterinfection is an ongoing challenge. This study, based on the development of a novel source attribution approach, provides the first results of source attribution inCampylobacter jejuniin France. A systematic analysis using gene-by-gene comparison of 884 genomes ofC. jejuniisolates, 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 inC. jejunitransmission dynamics.
authors.affiliation: Unit of Hygiene and Quality of Poultry & Pork Products, Laboratory of Ploufragan-Plouzané, French Agency for Food Environmental and Occupational Health & Safety (ANSES), Ploufragan, France.|University of Rennes 1, Rennes, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Thépault
authors.affiliation: The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Méric
authors.affiliation: Unit of Hygiene and Quality of Poultry & Pork Products, Laboratory of Ploufragan-Plouzané, French Agency for Food Environmental and Occupational Health & Safety (ANSES), Ploufragan, France.
authors.forename: Katell
authors.initials: K
authors.lastname: Rivoal
authors.affiliation: The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Pascoe
authors.affiliation: Swansea University Medical School, Institute of Life Science, Singleton Campus, Swansea, United Kingdom.
authors.forename: Leonardos
authors.initials: L
authors.lastname: Mageiros
authors.affiliation: Viral Genetics & Biosafety Unit, Laboratory of Ploufragan-Plouzané, French Agency for Food Environmental and Occupational Health & Safety (ANSES), Ploufragan, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Touzain
authors.affiliation: Unit of Hygiene and Quality of Poultry & Pork Products, Laboratory of Ploufragan-Plouzané, French Agency for Food Environmental and Occupational Health & Safety (ANSES), Ploufragan, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Rose
authors.affiliation: Viral Genetics & Biosafety Unit, Laboratory of Ploufragan-Plouzané, French Agency for Food Environmental and Occupational Health & Safety (ANSES), Ploufragan, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Béven
authors.affiliation: Unit of Hygiene and Quality of Poultry & Pork Products, Laboratory of Ploufragan-Plouzané, French Agency for Food Environmental and Occupational Health & Safety (ANSES), Ploufragan, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Chemaly
authors.affiliation: The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom s.k.sheppard@bath.ac.uk.|Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Sheppard
mesh_terms: D000818:Animals; D015373:Bacterial Typing Techniques; D002167:Campylobacter / Q000302:isolation & purification; D002169:Campylobacter Infections / Q000453:epidemiology* / Q000382:microbiology* / Q000635:transmission; D016123:Campylobacter jejuni / Q000145:classification / Q000235:genetics*; D002645:Chickens / Q000382:microbiology; D004197:Disease Reservoirs / Q000382:microbiology; D005516:Food Microbiology; D005602:France / Q000453:epidemiology; D005819:Genetic Markers; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D058885:Multilocus Sequence Typing; D012418:Ruminants / Q000382:microbiology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D005819:Genetic Markers
keywords: Campylobacter; food-borne diseases; gene-by-gene approach; genomics; source attribution