Rapid host switching in generalist <i>Campylobacter</i> strains erodes the signal for tracing human infections

Dearlove, Bethany L.; Cody, Alison J.; Pascoe, Ben; Méric, Guillaume; Wilson, Daniel J.; Sheppard, Samuel K.

doi:10.1038/ismej.2015.149

Cited by 130 publications

(153 citation statements)

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“…One potential way to improve power is to target signatures at other loci across the genome. While there is host-associated genetic variation, even in the genomes of host generalist C. jejuni lineages (30), using whole-genome MLST (35) data in an existing attribution model provided little additional power over seven-locus MLST (34). One explanation for this is the relative scarcity of host-segregating markers.…”

Section: Discussionmentioning

confidence: 99%

“…Self-attribution tests focused on chicken isolates (n ϭ 352) and ruminant isolates (n ϭ 59) as the source of the majority of isolates in this study and major reservoirs of human infection by C. jejuni. Furthermore, generalist ST-21 and ST-45 clonal complexes are common in these hosts but have been difficult to attribute to source using seven-locus MLST (23,26,29,34,49). Host attribution was performed using STRUCTURE software, a Bayesian model-based clustering method designed to infer population structure and attribute individuals to populations using multilocus genotype data (74).…”

Section: Methodsmentioning

confidence: 99%

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

Thépault

Méric

Rivoal

et al. 2017

Appl Environ Microbiol

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110

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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

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Thépault

Méric

Rivoal

et al. 2017

Appl Environ Microbiol

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110

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“…This distribution of rrpA and rrpB was also reflected in the analysis of the whole genome sequence data ( Figure 1 ) where red-labeled clonal complexes represent livestock-associated lineages and blue-labeled clonal complexes represent water and wildlife-associated lineages. It is, however, not always clear whether each clonal complex is associated with a single host as clonal complexes are regularly isolated from multiple animal species and thus attribution to a single host reservoir is difficult using MLST data alone (Dearlove et al, 2016). One example is the ST-48 complex that has been isolated from humans, cattle and sand from beaches (Dingle et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

The Campylobacter jejuni Oxidative Stress Regulator RrpB Is Associated with a Genomic Hypervariable Region and Altered Oxidative Stress Resistance

et al. 2016

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Campylobacter jejuni is the leading cause of bacterial foodborne diarrhoeal disease worldwide. Despite the microaerophilic nature of the bacterium, C. jejuni can survive the atmospheric oxygen conditions in the environment. Bacteria that can survive either within a host or in the environment like C. jejuni require variable responses to survive the stresses associated with exposure to different levels of reactive oxygen species. The MarR-type transcriptional regulators RrpA and RrpB have recently been shown to play a role in controlling both the C. jejuni oxidative and aerobic stress responses. Analysis of 3,746 C. jejuni and 486 C. coli genome sequences showed that whilst rrpA is present in over 99% of C. jejuni strains, the presence of rrpB is restricted and appears to correlate with specific MLST clonal complexes (predominantly ST-21 and ST-61). C. coli strains in contrast lack both rrpA and rrpB. In C. jejuni rrpB+ strains, the rrpB gene is located within a variable genomic region containing the IF subtype of the type I Restriction-Modification (hsd) system, whilst this variable genomic region in C. jejuni rrpB- strains contains the IAB subtype hsd system and not the rrpB gene. C. jejuni rrpB- strains exhibit greater resistance to peroxide and aerobic stress than C. jejuni rrpB+ strains. Inactivation of rrpA resulted in increased sensitivity to peroxide stress in rrpB+ strains, but not in rrpB- strains. Mutation of rrpA resulted in reduced killing of Galleria mellonella larvae and enhanced biofilm formation independent of rrpB status. The oxidative and aerobic stress responses of rrpB- and rrpB+ strains suggest adaptation of C. jejuni within different hosts and niches that can be linked to specific MLST clonal complexes.

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“…We are still far from that possibility, however, as only a few host-associated loci have been found in C. jejuni. Furthermore, the high prevalence and wide distribution of so-called "generalist lineages" complicate source attribution, due to their lacking genetic responses to host colonization (31). For instance, Dearlove and colleagues found that ST-21 CC and ST-45 CC undergo rapid host switching, which appears to erode the development of host signals; therefore, WGS appears no more informative than 7-gene MLST in defining the source of infections for generalist lineages (31).…”

Section: Application Of Wgs In C Jejuni Source Attribution and Analymentioning

confidence: 99%

Whole-Genome Sequencing in Epidemiology of Campylobacter jejuni Infections

2017

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This review describes the current state of knowledge regarding the application of whole-genome sequencing (WGS) in the epidemiology of Campylobacter jejuni, the leading cause of bacterial gastroenteritis worldwide. We describe how WGS has increased our understanding of the evolutionary and epidemiological dynamics of this pathogen and how WGS has the potential to improve surveillance and outbreak detection. We have identified hurdles to the full implementation of WGS in public health settings. Despite these challenges, we think that ample evidence is available to support the benefits of integrating WGS into the routine monitoring of C. jejuni infections and outbreak investigations.KEYWORDS foodborne pathogens, genome analysis, molecular subtyping, surveillance studies T he ability to conduct epidemiological investigations and to intervene to control and to prevent foodborne and environmentally transmitted diseases is a major task of public health authorities. The identification, over a short period of time, of a sudden increase in the number of expected cases of a disease in a population in a limited geographical area (point-source outbreak) or clusters of cases with a presumptive common source not necessarily clustered geographically (diffuse outbreak) depends on knowledge of the baseline infectious state of the population regarding that disease, which is usually acquired through surveillance. In this regard, identifying epidemiologically linked cases and differentiating them from concurrent sporadic incidences are essential for risk assessment, outbreak investigations, and source attribution for foodborne pathogens. These processes have relied increasingly on traditional epidemiological investigations supplemented with molecular subtyping of the etiological agent, and no method offers a higher degree of resolution than whole-genome sequencing (WGS). The recent development of high-throughput sequencing technologies for WGS (i.e., next-generation sequencing [NGS]) has resulted in large-scale sequencing of various pathogens. Allowing the detection of all possible epidemiologically significant variations between strains (1), WGS is progressively replacing traditional typing methods (serotyping, phenotyping, pulsed-field gel electrophoresis [PFGE], and amplified fragment length polymorphism [AFLP] analysis) and sequence-based investigations (PCR-based methods). Moreover, the declining costs of NGS and the availability of benchtop analyzers are increasingly facilitating the application of WGS for routine surveillance and outbreak investigations of bacterial and viral infectious diseases by public health authorities (2). As a result, WGS analysis is currently being used in several countries for real-time surveillance of Listeria monocytogenes and Salmonella enterica (http://www.fda.gov/Food/FoodScience Research/WholeGenomeSequencingProgramWGS) (3), and similar approaches for other foodborne pathogens are expected to come into use shortly. Campylobacter jejuni is one of the most frequent causes of bacterial g...

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Rapid host switching in generalist Campylobacter strains erodes the signal for tracing human infections

Cited by 130 publications

References 49 publications

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

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

The Campylobacter jejuni Oxidative Stress Regulator RrpB Is Associated with a Genomic Hypervariable Region and Altered Oxidative Stress Resistance

Whole-Genome Sequencing in Epidemiology of Campylobacter jejuni Infections

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