Analysis of Campylobacter jejuni infection in the gnotobiotic piglet and genome-wide identification of bacterial factors required for infection

Campylobacter jejuni is a common cause of diarrheal disease worldwide. Human infection typically occurs through the ingestion of contaminated poultry products. We previously demonstrated that an attenuated Escherichia coli live vaccine strain expressing the C. jejuni N-glycan on its surface reduced the Campylobacter load in more than 50% of vaccinated leghorn and broiler birds to undetectable levels (responder birds), whereas the remainder of the animals was still colonized (non-responders). To understand the underlying mechanism, we conducted three vaccination and challenge studies using 135 broiler birds and found a similar responder/non-responder effect. Subsequent genome-wide association studies (GWAS), analyses of bird sex and levels of vaccine-induced IgY responses did not correlate with the responder versus non-responder phenotype. In contrast, antibodies isolated from responder birds displayed a higher Campylobacter-opsonophagocytic activity when compared to antisera from non-responder birds. No differences in the N-glycome of the sera could be detected, although minor changes in IgY glycosylation warrant further investigation. As reported before, the composition of the microbiota, particularly levels of OTU classified as Clostridium spp., Ruminococcaceae and Lachnospiraceae are associated with the response. Transplantation of the cecal microbiota of responder birds into new birds in combination with vaccination resulted in further increases in vaccine-induced antigen-specific IgY responses when compared to birds that did not receive microbiota transplants. Our work suggests that the IgY effector function and microbiota contribute to the efficacy of the E. coli live vaccine, information that could form the basis for the development of improved vaccines targeted at the elimination of C. jejuni from poultry.

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Genome-wide fitness analyses of the foodborne pathogen Campylobacter jejuni in in vitro and in vivo models

Scientific Reports ◽

10.1038/s41598-017-01133-4 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 15

Author(s):

Stefan P. de Vries ◽

Srishti Gupta ◽

Abiyad Baig ◽

Elli Wright ◽

Amy Wedley ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Foodborne Pathogen ◽

In Vivo Models ◽

Genome Wide

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A Genome-Wide Association Study to Identify Diagnostic Markers for Human Pathogenic Campylobacter jejuni Strains

Frontiers in Microbiology ◽

10.3389/fmicb.2017.01224 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 21

Author(s):

Cody J. Buchanan ◽

Andrew L. Webb ◽

Steven K. Mutschall ◽

Peter Kruczkiewicz ◽

Dillon O. R. Barker ◽

...

Keyword(s):

Association Study ◽

Campylobacter Jejuni ◽

Genome Wide Association Study ◽

Diagnostic Markers ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome

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An RNase III processed, antisense RNA pair regulates a Campylobacter jejuni colonization factor

10.1101/2021.03.19.434396 ◽

2021 ◽

Author(s):

Sarah L Svensson ◽

Cynthia M. Sharma

Keyword(s):

Campylobacter Jejuni ◽

Stress Responses ◽

Foodborne Pathogen ◽

Rnase E ◽

Rnase Iii ◽

Cis Acting ◽

Colonization Factor ◽

Genome Wide ◽

Intergenic Regions ◽

Genomic Locations

Small RNAs (sRNAs) are emerging as important and diverse post-transcriptional gene expression regulators in bacterial stress responses and virulence. While originally identified mainly in intergenic regions, genome-wide approaches have revealed sRNAs encoded in diverse contexts, such as processed from parental transcripts by RNase E. Despite its well-known roles in rRNA processing, RNA decay, cleavage of sRNA-mRNA duplexes, the role of RNase III in sRNA biogenesis is less well understood. Here, we show that a pair of cis-encoded sRNAs (CJnc190 and CJnc180) are processed by RNase III in the foodborne pathogen Campylobacter jejuni. While CJnc180 processing requires CJnc190, RNase III cleaves an intramolecular duplex in CJnc190, independent of CJnc180. Moreover, we demonstrate that CJnc190 directly represses translation of the colonization factor PtmG by binding its G-rich ribosome binding site, and show that CJnc180 is a cis-acting antagonist of CJnc190, thereby indirectly affecting ptmG regulation. Our results expand the diversity of known genomic locations of bacterial sRNA sponges and highlight a role for bacterial RNase III that parallels miRNA processing by related eukaryotic Dicer and Drosha.

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

10.7287/peerj.preprints.2300v1 ◽

2016 ◽

Cited By ~ 1

Author(s):

Koji Yahara ◽

Guillaume Méric ◽

Aidan J Taylor ◽

Stefan PW de Vries ◽

Susan Murray ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Genome Wide Association Study ◽

Human Infection ◽

Genome Wide Association ◽

Processing Chain ◽

Genome Wide ◽

A Genome ◽

Poultry Processing ◽

Pathogen Populations ◽

Oxidative Respiration

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 7,343 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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Genome-Wide Fitness Analyses of the Foodborne PathogenCampylobacter jejuniinIn VitroandIn VivoModels

10.1101/085720 ◽

2016 ◽

Cited By ~ 1

Author(s):

Stefan P. W. de Vries ◽

Srishti Gupta ◽

Abiyad Baig ◽

Elli Wright ◽

Amy Wedley ◽

...

Keyword(s):

Life Cycle ◽

Low Temperature ◽

Campylobacter Jejuni ◽

Intervention Strategies ◽

Gene Inactivation ◽

Effective Control ◽

Epithelial Tissue ◽

Human Gut ◽

Growth And Survival ◽

Genome Wide

AbstractInfection byCampylobacteris recognised as the most common cause of foodborne bacterial illness worldwide. Faecal contamination of meat, especially chicken, during processing represents a key route of transmission to humans. There is currently no licenced vaccine and noCampylobacter-resistant chickens. In addition, preventative measures aimed at reducing environmental contamination and exposure of chickens toCampylobacter jejuni(biosecurity) have been ineffective. There is much interest in the factors/mechanisms that driveC. jejunicolonisation and infection of animals, and survival in the environment. It is anticipated that understanding these mechanisms will guide the development of effective intervention strategies to reduce the burden ofC. jejuniinfection. Here we present a comprehensive analysis ofC. jejunifitness during growth and survival within and outside hosts. A comparative analysis of transposon (Tn) gene inactivation libraries in threeC. jejunistrains by Tn-seq demonstrated that a large proportion, 331 genes, of theC. jejunigenome is dedicated to (in vitro) growth. An extensive Tn library inC. jejuniM1cam (~10,000 mutants) was screened for the colonisation of commercial broiler chickens, survival in houseflies and under nutrient-rich and–poor conditions at low temperature, and infection of human gut epithelial cells. We reportC. jejunifactors essential throughout its life cycle and we have identified genes that fulfil important roles across multiple conditions, includingmaf3, fliW, fliD, pflBandcapM, as well as novel genes uniquely implicated in survival outside hosts. Taking a comprehensive screening approach has confirmed previous studies, that the flagella are central to the ability ofC. jejunito interact with its hosts. Future efforts should focus on how to exploit this knowledge to effectively control infections caused byC. jejuni.Author SummaryCampylobacter jejuniis the leading bacterial cause of human diarrhoeal disease.C. jejuniencounters and has to overcome a wide range of “stress” conditions whilst passing through the gastrointestinal tract of humans and other animals, during processing of food products, on/in food and in the environment. We have taken a comprehensive approach to understand the basis ofC. jejunigrowth and within/outside host survival, with the aim to inform future development of intervention strategies. Using a genome-wide transposon gene inactivation approach we identified genes core to the growth ofC. jejuni. We also determined genes that were required during the colonisation of chickens, survival in the housefly and under nutrient-rich and –poor conditions at low temperature, and during interaction with human gut epithelial tissue culture cells. This study provides a comprehensive dataset linkingC. jejunigenes to growth and survival in models relevant to its life cycle. Genes important across multiple models were identified as well as genes only required under specific conditions. We identified that a large proportion of theC. jejunigenome is dedicated to growth and that the flagella fulfil a prominent role in the interaction with hosts. Our data will aid development of effective control strategies.

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Genome-Wide Prediction of Potential Vaccine Candidates for Campylobacter jejuni Using Reverse Vaccinology

Interdisciplinary Sciences Computational Life Sciences ◽

10.1007/s12539-017-0260-5 ◽

2017 ◽

Vol 11 (3) ◽

pp. 337-347 ◽

Cited By ~ 5

Author(s):

Richa Jain ◽

Sarita Singh ◽

Santosh kumar Verma ◽

Ankit Jain

Keyword(s):

Campylobacter Jejuni ◽

Reverse Vaccinology ◽

Vaccine Candidates ◽

Genome Wide ◽

Potential Vaccine

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Genome-wide insights into population structure and host specificity of Campylobacter jejuni

Scientific Reports ◽

10.1038/s41598-021-89683-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lennard Epping ◽

Birgit Walther ◽

Rosario M. Piro ◽

Marie-Theres Knüver ◽

Charlotte Huber ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Animal Species ◽

Strong Association ◽

Ecological Niches ◽

Genome Maintenance ◽

Host Animal ◽

Host Preferences ◽

Specific Host ◽

Genome Wide ◽

Core Genes

AbstractThe zoonotic pathogen Campylobacter jejuni is among the leading causes of foodborne diseases worldwide. While C. jejuni colonises many wild animals and livestock, persistence mechanisms enabling the bacterium to adapt to host species' guts are not fully understood. In order to identify putative determinants influencing host preferences of distinct lineages, bootstrapping based on stratified random sampling combined with a k-mer-based genome-wide association was conducted on 490 genomes from diverse origins in Germany and Canada. We show a strong association of both the core and the accessory genome characteristics with distinct host animal species, indicating multiple adaptive trajectories defining the evolution of C. jejuni lifestyle preferences in different ecosystems. Here, we demonstrate that adaptation towards a specific host niche ecology is most likely a long evolutionary and multifactorial process, expressed by gene absence or presence and allele variations of core genes. Several host-specific allelic variants from different phylogenetic backgrounds, including dnaE, rpoB, ftsX or pycB play important roles for genome maintenance and metabolic pathways. Thus, variants of genes important for C. jejuni to cope with specific ecological niches or hosts may be useful markers for both surveillance and future pathogen intervention strategies.

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