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

Abstract

Campylobacter 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 Campylobacter jejuni 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 C. jejuni 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 nationalscale attribution modeling to account for differences in production, behavior, and food consumption.IMPORTANCE Accurately quantifying the relative contribution of different host reservoirs to human Campylobacter 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 Campylobacter jejuni in France. A systematic analysis using gene-by-gene comparison of 884 genomes of C. jejuni 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

AB_SA: Tracing the source of bacterial strains based on accessory genes. Application toSalmonellaTyphimurium environmental strains

“…Consistent with previously published source attribution studies, the overall self-attribution accuracy of this study was 75-80% (17; 18; 12).…”

“…These approaches have been successfully applied for source attribution of human sporadic strains for Campylobacter spp. (11; 12), Salmonella spp. and Listeria monocytogenes (13) .…”

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

“…Contrasting evidence of HGT with quantitative information about the transmission of resistant bacteria between hosts would be extremely useful for understanding the dissemination of AMR among isolates from different habitats. In Campylobacter , studies have attempted to estimate the number of strains excreted into the environment by different animals (Ogden et al ., ) and attribute the source of human infection to livestock (especially poultry) reservoirs (Sheppard et al ., ; Thépault et al ., , ). However, these large‐scale probabilistic studies are utterly underpowered for investigating the almost infinite number of possible transmission events, where the survival and proliferation of a single strain in a new niche could lead to the transfer of AMR genes between hosts and environments.…”

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

“…This host‐associated genetic structure can be informative for understanding the evolution of C. jejuni (Dearlove et al., ), but can also be used in a more practical way to identify the source of isolates causing human infection by identifying genomic signatures (resulting from adaptation or drift) in the infecting isolate that are associated with populations in particular reservoir hosts (Sheppard et al., ; Wilson et al., ). Quantitative source attribution models, based upon the probability that a particular clinical isolate originated in different reservoirs, have been widely used to estimate the risk of human infection from different food production animals and other sources (Colles et al., ; French et al., ; Griekspoor et al., ; Mullner et al., ; Roux et al., ; Sheppard et al., ; Thepault et al., ; Viswanathan et al., ) and have informed intervention strategies and public health policy (Cody et al., , ).…”