title: Passage of Campylobacter jejuni through the chicken reservoir or mice promotes phase variation in contingency genes Cj0045 and Cj0170 that strongly associates with colonization and disease in a mouse model.
abstract: Human illness due to Camplyobacter jejuni infection is closely associated with consumption of poultry products. We previously demonstrated a 50 % shift in allele frequency (phase variation) in contingency gene Cj1139 (wlaN) during passage of C. jejuni NCTC11168 populations through Ross 308 broiler chickens. We hypothesized that phase variation in contingency genes during chicken passage could promote subsequent colonization and disease in humans. To test this hypothesis, we passaged C. jejuni strains NCTC11168, 33292, 81-176, KanR4 and CamR2 through broiler chickens and analysed the ability of passaged and non-passaged populations to colonize C57BL6 IL-10-deficient mice, our model for human colonization and disease. We utilized fragment analysis and nucleotide sequence analysis to measure phase variation in contingency genes. Passage through the chicken reservoir promoted phase variation in five specific contingency genes, and these 'successful' populations colonized mice. When phase variation did not occur in these same five contingency genes during chicken passage, these 'unsuccessful' populations failed to colonize mice. Phase variation during chicken passage generated small insertions or deletions (indels) in the homopolymeric tract (HT) in contingency genes. Single-colony isolates of C. jejuni strain KanR4 carrying an allele of contingency gene Cj0170 with a10G HT colonized mice at high frequency and caused disease symptoms, whereas single-colony isolates carrying the 9G allele failed to colonize mice. Supporting results were observed for the successful 9G allele of Cj0045 in strain 33292. These data suggest that phase variation in Cj0170 and Cj0045 is strongly associated with mouse colonization and disease, and that the chicken reservoir can play an active role in natural selection, phase variation and disease.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Joo-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Artymovich
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Hall
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Smith
authors.affiliation: Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Fulton
authors.affiliation: National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Bell
authors.affiliation: National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Dybas
authors.affiliation: Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA.|National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Mansfield
authors.affiliation: Center for Statistical Training and Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Tempelman
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Wilson
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA.|National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA.|Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Linz
mesh_terms: D000483:Alleles; D000818:Animals; D002169:Campylobacter Infections / Q000382:microbiology*; D016123:Campylobacter jejuni / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D002645:Chickens / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005787:Gene Frequency; D054643:INDEL Mutation; D051379:Mice; D008810:Mice, Inbred C57BL; D012692:Serial Passage; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D037521:Virulence Factors