Multi-Omics Approach Reveals the Potential Core Vaccine Targets for the Emerging Foodborne Pathogen Campylobacter jejuni

Abstract

Campylobacter jejuni is a leading cause of bacterial gastroenteritis in humans around the world. The emergence of bacterial resistance is becoming more serious; therefore, development of new vaccines is considered to be an alternative strategy against drug-resistant pathogen. In this study, we investigated the pangenome of 173 C. jejuni strains and analyzed the phylogenesis and the virulence factor genes. In order to acquire a high-quality pangenome, genomic relatedness was firstly performed with average nucleotide identity (ANI) analyses, and an open pangenome of 8,041 gene families was obtained with the correct taxonomy genomes. Subsequently, the virulence property of the core genome was analyzed and 145 core virulence factor (VF) genes were obtained. Upon functional genomics and immunological analyses, five core VF proteins with high antigenicity were selected as potential core vaccine targets for humans. Furthermore, functional annotations indicated that these proteins are involved in important molecular functions and biological processes, such as adhesion, regulation, and secretion. In addition, transcriptome analysis in human cells and pig intestinal loop proved that these vaccine target genes are important in the virulence of C. jejuni in different hosts. Comprehensive pangenome and relevant animal experiments will facilitate discovering the potential core vaccine targets with improved efficiency in reverse vaccinology. Likewise, this study provided some insights into the genetic polymorphism and phylogeny of C. jejuni and discovered potential vaccine candidates for humans. Prospective development of new vaccines using the targets will be an alternative to the use of antibiotics and prevent the development of multidrug-resistant C. jejuni in humans and even other animals.

The Distribution of Campylobacter jejuni Virulence Genes in Genomes Worldwide Derived from the NCBI Pathogen Detection Database

“…Curiously, in this study, a higher recovery rate of flaA and flaB previously amplified by a conventional PCR was observed via WGS screening, showing the better resolution of this technique for virulence detection [73]. In a genome-wide association study with C.jejuni isolates from Poland, the authors displayed similar results, reporting that the majority of the virulence genes, with rare exceptions such as flaA, flaB, or flaE, were evenly distributed throughout the genomes of all the STs under study [74]. Finally, in a multi-omics approach study that revealed the potential core vaccine targets for C. jejuni, flaA and flaB were not found within the core or essential core virulome of 173 strains [75].…”

Comparative genomics of Campylobacter jejuni from clinical campylobacteriosis stool specimens

“…Currently, the most discriminatory method for investigating strain diversity is by using whole genome sequencing (WGS) and analysing the complete genome [ 22 , 23 ]. Cao et al [ 24 ] estimated that the C. jejuni pangenome consisted of 900 core genes and 4621 accessory genes, based on 173 C. jejuni strains, whilst Rossi et al . identified 678 core and 2117 accessory genes based on 6526 C. jejuni isolates [ 25 ].…”

“…The different sizes of the pangenomes between these studies can be attributed to the different genomes, software and cut-offs used, but both highlight that C. jejuni has a relatively small core genome compared to its large accessory genome. The genetic variation of the genome within the species is thought to be linked to some strains carrying genes associated with increased pathogenicity in human infection [ 24 ]. Pathogenicity genes associated with the organism’s ability to survive in adverse conditions and possible host specificity have been reported [ 24 ].…”

“…The genetic variation of the genome within the species is thought to be linked to some strains carrying genes associated with increased pathogenicity in human infection [ 24 ]. Pathogenicity genes associated with the organism’s ability to survive in adverse conditions and possible host specificity have been reported [ 24 ]. The overall diversity of C. jejuni therefore requires that a large proportion of the population is analysed in epidemiological investigations [ 24 , 26 ].…”

Phylogenetic Association and Genetic Factors in Cold Stress Tolerance in Campylobacter jejuni

“…Comparing the genome sequences between the two clusters led to the identification of 58 genes present in C. jejuni strains in the cold stress-tolerant cluster and absent from the strains in the cold stress-sensitive cluster (Table 1). Based on previous efforts to identify genes involved in human campylobacteriosis (38, 39), interestingly, most of the 58 genes unique to the cold stress-tolerant cluster are present only in clinical isolates and absent from nonclinical isolates, including kpsA (encoding potassium-transporting ATPase subunit), uxaA (encoding UxaA family hydrolase), cfrA (encoding ferric enterobactin receptor) and others. Although it remains unexplained whether these genes are related to the pathogenicity of C. jejuni , it can be speculated that cold stress-tolerant strains are more likely to cause human infection than cold stress-sensitive strains because cold tolerance enables C. jejuni to survive on poultry meat, the primary cause of campylobacteriosis, in the food supply chain and increases the chances of human exposure to C. jejuni .…”