Comparative Variation within the Genome of Campylobacter jejuni NCTC 11168 in Human and Murine Hosts

Dallas K Thomas,Eduardo N Taboada,Richard R E Uwiera,L Brent Selinger,D Wade Abbott,G Douglas Inglis,Abdul G Lone

doi:10.1371/journal.pone.0088229

Abstract

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.

Highlights

Campylobacteriosis incited by C. jejuni is a prevalent enteric disease of people
CGF40 subtyping revealed that the isolates were indistinguishable from each other, and from National Collection of Type Cultures (NCTC) 11168-GSv and NCTC 11168-V26; the isolates from the stool and reference strains were positive for all 40 loci within the comparative genomic fingerprint (CGF) assay
We observed that a variant strain of C. jejuni NCTC 11168-GSv infected and incited severe enteritis in a human being

Summary

Introduction

Campylobacteriosis incited by C. jejuni is a prevalent enteric disease of people. The epidemiology of campylobacteriosis is poorly understood at present, and the source attribution hypothesis suggests that some genetic lineages of C. jejuni exist that define host adaptation. This hypothesis is consistent with observations that certain genetic lineages of C. jejuni are commonly associated with diarrheic human beings but not with non-human hosts [1]. The application of multilocus sequence typing in conjunction with source attribution models has been used to link various reservoirs of C. jejuni with human infections [2,3,4,5,6]. The degree to which host specificity exists across various sub-lineages (i.e. Sequence Types or STs) in the C. jejuni population is unclear. Whether genotyping schemes with higher resolution such as comparative genomic fingerprint (CGF) subtyping [1,8] will yield data with improved host specificity remains to be determined

Methods

Results

Conclusion