Genome-wide association study identifies vitamin B5 biosynthesis as a host specificity factor in Campylobacter

Genome-wide association study identifies vitamin B₅ biosynthesis as a host specificity factor in Campylobacter

1. Samuel K. Sheppard^a,^b,¹,
2. Xavier Didelot^c,
3. Guillaume Meric^b,
4. Alicia Torralbo^d,
5. Keith A. Jolley^a,
6. David J. Kelly^e,
7. Stephen D. Bentley^f,^g,
8. Martin C. J. Maiden^a,
9. Julian Parkhill^f, and
10. Daniel Falush^h

Author Affiliations

1. Edited by W. Ford Doolittle, Dalhousie University, Halifax, Canada, and approved June 3, 2013 (received for review March 22, 2013)

Abstract

Genome-wide association studies have the potential to identify causal genetic factors underlying important phenotypes but have rarely been performed in bacteria. We present an association mapping method that takes into account the clonal population structure of bacteria and is applicable to both core and accessory genome variation. Campylobacter is a common cause of human gastroenteritis as a consequence of its proliferation in multiple farm animal species and its transmission via contaminated meat and poultry. We applied our association mapping method to identify the factors responsible for adaptation to cattle and chickens among 192 Campylobacter isolates from these and other host sources. Phylogenetic analysis implied frequent host switching but also showed that some lineages were strongly associated with particular hosts. A seven-gene region with a host association signal was found. Genes in this region were almost universally present in cattle but were frequently absent in isolates from chickens and wild birds. Three of the seven genes encoded vitamin B₅ biosynthesis. We found that isolates from cattle were better able to grow in vitamin B₅-depleted media and propose that this difference may be an adaptation to host diet.

• evolution
• genomics
• host adaptation
• transmission ecology

Footnotes

• ¹To whom correspondence should be addressed. E-mail: s.k.sheppard@swansea.ac.uk.

• Author contributions: S.K.S., X.D., and D.F. designed research; S.K.S., X.D., G.M., A.T., S.D.B., and J.P. performed research; S.K.S., X.D., K.A.J., M.C.J.M., and J.P. contributed new reagents/analytic tools; S.K.S., X.D., G.M., D.J.K., and D.F. analyzed data; and S.K.S., X.D., and D.F. wrote the paper.
• The authors declare no conflict of interest.
• This article is a PNAS Direct Submission.
• Data deposition: Genome sequence data for isolates that were sequenced in this study have been deposited with Dryad, http://datadryad.org/. The data will be available in 48 h from the date of resubmission with the following doi:10.5061/dryad.28n35. Data will also be available via PubMLST, http://pubmlst.org/campylobacter/.
• This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1305559110/-/DCSupplemental.