Faculty Research and Publications

Permanent URI for this community

https://opus.uleth.ca/handle/10133/843

Browse

Browsing Faculty Research and Publications by Author "Abbott, D. Wade"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Comparative variation within the genome of Campylobacter jejuni NCTC 11168 in human and murine hosts
    (Public LIbrary of Science, 2014) Thomas, Dallas K.; Lone, Abdul G.; Selinger, L. Brent; Taboada, Eduardo N.; Uwiera, Richard R.E.; Abbott, D. Wade; Inglis, G. Douglas
    Campylobacteriosis incited by C. jejuni is a significant enteric disease of human beings. A person working with two reference strains of C. jejuni National Collection of Type Cultures (NCTC) 11168 developed symptoms of severe enteritis including bloody diarrhea. The worker was determined to be infected by C. jejuni . In excess of 50 isolates were recovered from the worker’s stool. All of the recovered isolates and the two reference strains were indistinguishable from each other based on comparative genomic fingerprint subtyping. Whole genome sequence analysis indicated that the worker was infected with a C. jejuni NCTC 11168 obtained from the American Type Culture Collection; this strain (NCTC 11168-GSv) is the genome sequence reference. After passage through the human host, major genetic changes including indel mutations within twelve contingency loci conferring phase variations were detected in the genome of C. jejuni . Specific and robust single nucleotide polymorphism (SNP) changes in the human host were also observed in two loci (Cj0144c, Cj1564). In mice inoculated with an isolate of C. jejuni NCTC 11168-GSv from the infected person, the isolate underwent further genetic variation. At nine loci, mutations specific to inoculated mice including five SNP changes were observed. The two predominant SNPs observed in the human host reverted in mice. Genetic variations occurring in the genome of C. jejuni in mice corresponded to increased densities of C. jejuni cells associated with cecal mucosa. In conclusion, C. jejuni NCTC 11168-GSv was found to be highly virulent in a human being inciting severe enteritis. Host-specific mutations in the person with enteritis occurred/were selected for in the genome of C. jejuni , and many were not maintained in mice. Information obtained in the current study provides new information on host-specific genetic adaptation by C. jejuni .
  • Thumbnail Image
    Item
    A genome-wide association study to identify diagnostic markers for human pathogenic Campylobacter jejuni strains
    (Frontiers Media, 2017) Buchanan, Cody J.; Webb, Andrew L.; Mutschall, Steven K.; Kruczkiewicz, Peter; Barker, Dillon Oliver Reese; Hetman, Benjamin M.; Gannon, Victor P. J.; Abbott, D. Wade; Thomas, James E.; Inglis, G. Douglas; Taboada, Eduardo N.
    Campylobacter jejuni is a leading human enteric pathogen worldwide and despite an improved understanding of its biology, ecology, and epidemiology, limited tools exist for identifying strains that are likely to cause disease. In the current study, we used subtyping data in a database representing over 24,000 isolates collected through various surveillance projects in Canada to identify 166 representative genomes from prevalent C. jejuni subtypes for whole genome sequencing. The sequence data was used in a genome-wide association study (GWAS) aimed at identifying accessory gene markers associated with clinically related C. jejuni subtypes. Prospective markers (n=28) were then validated against a large number (n=3,902) of clinically associated and non-clinically associated genomes from a variety of sources. A total of 25 genes, including six sets of genetically linked genes, were identified as robust putative diagnostic markers for clinically related C. jejuni subtypes. Although some of the genes identified in this study have been previously shown to play a role in important processes such as iron acquisition and vitamin B5 biosynthesis, others have unknown function or are unique to the current study and warrant further investigation. As few as four of these markers could be used in combination to detect up to 90% of clinically associated isolates in the validation dataset, and such markers could form the basis for a screening assay to rapidly identify strains that pose an increased risk to public health. The results of the current study are consistent with the notion that specific groups of C. jejuni strains of interest are defined by the presence of specific accessory genes.