An investigation into the genetic diversity of the food-borne pathogen campylobacter jejuni using DNA microarrays

Doctoral thesis English OPEN
Champion, Olivia Lucy

Despite being the principal bacterial cause of gastroenteritis world wide, the\ud epidemiology of Campylobacter jejuni is poorly understood. This is largely because\ud the proportion of human disease caused by different sources of infection is unknown.\ud In this study a diverse strain collection was selected comprising of 91C. jejuni isolates\ud from diverse animal and environmental ecological niches as well as clinical isolates\ud from patients representing a range of disease outcomes. Whole genome comparisons\ud were performed by DNA microarray analysis with the dual aim of identifying genetic\ud markers specific to strains from different ecological niches and identifying novel\ud virulence determinants.\ud A new phylogenomic technique for the analysis of DNA microarray data was\ud developed combining Bayesian algorithms to model phylogeny based on whole\ud genome data with parsimony based algorithms to identify the key genes contributing\ud to the clade formations. This method revealed a previously undetected C. jejuni\ud population structure comprising two main clades, a "chicken clade" and a "nonchicken\ud clade". These statistically supported clades differentiated strains from distinct\ud ecological niches with 94% of strains isolated from chickens and 41% of clinical\ud isolates contained within the "chicken clade". C. jejuni isolates from ovine, bovine\ud and sand isolates also formed distinct clades within the "non-chicken clade". Key\ud genes contributing to the distinction of strains from one ecological niche from another\ud were identified. In particular a putative glycosylation islet cj 1321-cj 1326 was found\ud to be present in strains within the "chicken clade" but absent or divergent from strains\ud in the "non-chicken clade', a result validated by peR screening. This locus represents\ud a potential genetic marker of C. jejuni strains of avian origin.\ud The DNA microarray data analysis method described in this study may be used to\ud study other bacterial pathogens facilitating the identification of bacterial phylogenies\ud and genetic markers associated with specific phenotypes.
  • References (63)
    63 references, page 1 of 7

    Aspinall, G.O., McDonald, A.G., and Pang, H. (1992) Structures of the 0 chains from lipopolysaccharides of Campylobacter jejuni serotypes 0:23 and 0:36. Carbohydr Res 231: 13-30.

    Aspinall, G.O., Fujimoto, S., McDonald, A.G., Pang, H., Kurjanczyk, L.A., and Penner, J.L. (1994a) Lipopolysaccharides from Campylobaeter jejuni associated with GuillainBarre syndrome patients mimic human gangliosides in structure. Infect Immun 62: 2122-2125.

    Aspinall, G.O., McDonald, A.G., and Pang, H. (1994b) Lipopolysaccharides of Campylobacter jejuni serotype 0:19: structures of 0 antigen chains from the serostrain and two bacterial isolates from patients with the GuillainBarre syndrome. Biochemistry 33: 250-255.

    Bacon, D.J., Szymanski, C.M., Burr, D.H., Silver, R.P., Aim, R.A., and Guerry, P. (2001) A phase-variable capsule is involved in virulence of Campylobacter jejuni 81-176. Mol Microbio/40: 769-777.

    Benz, I., and Schmidt, M.A. (2001) Glycosylation with heptose residues mediated by the aah gene product is essential for adherence of the AIDA-I adhesin. Mol Microbio/40: 1403-1413.

    Black, R.E., Levine, M.M., Clements, M.L., Hughes, T.P., and Blaser, M.J. (1988) Experimental Campylobacter jejuni infection in humans. J Infect Dis 157: 472-479.

    Bonfield, J.K., Smith, K., and Staden, R. (1995) A new DNA sequence assembly program. Nucleic Acids Res 23: 4992-4999.

    Brooke, J.S., and Valvano, M.A. (1996) Biosynthesis of inner core lipopolysaccharide in enteric bacteria identification and characterization of a conserved phosphoheptose isomerase. J BioI Chem 271: 3608-3614.

    DeShazer, D., Brett, P.J., and Woods, D.E. (1998) The type II O-antigenic polysaccharide moiety of Burkholderia pseudomallei lipopolysaccharide is required for serum resistance and virulence. Mol Microbial 3D: 1081-1100.

    Dillard, J.P., and Yother, J. (1994) Genetic and molecular characterization of capsular polysaccharide biosynthesis in Streptococcus pneumoniae type 3. Mol Microbio/12: 959- 972.

  • Metrics
    views in OpenAIRE
    views in local repository
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    LSHTM Research Online - IRUS-UK 0 53
Share - Bookmark