title: Standing genetic variation in contingency loci drives the rapid adaptation of Campylobacter jejuni to a novel host.
abstract: The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10(-/-) mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64 Mb genome to 200-500 X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host.
authors.affiliation: Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: John P
authors.initials: JP
authors.lastname: Jerome
authors.forename: Julia A
authors.initials: JA
authors.lastname: Bell
authors.forename: Anne E
authors.initials: AE
authors.lastname: Plovanich-Jones
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Barrick
authors.forename: C Titus
authors.initials: CT
authors.lastname: Brown
authors.forename: Linda S
authors.initials: LS
authors.lastname: Mansfield
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D002169:Campylobacter Infections; D016123:Campylobacter jejuni / Q000235:genetics* / Q000472:pathogenicity*; D014644:Genetic Variation; D016680:Genome, Bacterial / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D016366:Open Reading Frames; D012692:Serial Passage; D014774:Virulence