A genome-wide association study to identify diagnostic markers for human pathogenic campylobacter jejuni strains

Citation

Buchanan, C.J., Webb, A.L., Mutschall, S.K., Kruczkiewicz, P., Barker, D.O.R., Hetman, B.M., Gannon, V.P.J., Abbott, D.W., Thomas, J.E., Inglis, G.D., Taboada, E.N. (2017). A genome-wide association study to identify diagnostic markers for human pathogenic campylobacter jejuni strains, 8(JUN), http://dx.doi.org/10.3389/fmicb.2017.01224

Plain language summary

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.

Abstract

© 2017 Buchanan, Webb, Mutschall, Kruczkiewicz, Barker, Hetman, Gannon, Abbott, Thomas, Inglis and Taboada.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.

Publication date

2017-06-30