| Özet: | <p>The bacterium Campylobacter jejuni is responsible for a substantial burden of human
disease. It has a wide host and environmental distribution. The ecology in non-human hosts
has been studied, in particular for farm animals, but the relationship between different host
and environmental niches, including the extent to which host and geography are associated
with genetic differentiation, is uncertain. Open epidemiological questions include the
largely unexplained summer peaks in many temperate countries, apparent paucity of
outbreaks despite a high incidence of foodborne infection, and uncertainty in the
quantitative contributions of different sources to human infection. Bacterial subtyping has
not made a substantial contribution to the ecology or epidemiology of this species. This
thesis applied a housekeeping gene multilocus sequence typing scheme, complemented
with more variable antigen genes, in epidemiological and ecological studies of C. jejuni.</p>
<p>These studies identified a large contribution of one clonal group to the high level of human
infection during summer along with a similar seasonal rise in relative prevalence for this
Glade in poultry meat, and the association of other phenotypic characteristics with the Glade.
A lack of geographical variation between distant populations within England contrasted
with substantial differences at international level. Genetic differentiation by host species
exceeded geographic and temporal effects and showed the potential of using multilocus
genotype to attribute human infection to animal host sources. Recombination played a
major role in the generation of this genetic differentiation, which finding informed the use
of alleles rather than summary measures of genotype in population assignment of C. jejuni.
Using fine typing with porA and flaA gene fragments to produce higher discrimination than
previously applied allowed the identification of genotypic clusters, demonstrated emergent
clades within the poultry industry and human disease, and confirmed empirically the
predictions from theoretical work that even more highly discriminatory methods will be
needed to reliably identify outbreaks and their specific source using genotype.</p>
<p>This work has thus exploited the of integration multilocus sequencing in studies of the
epidemiology and ecology of C. jejuni, developed analytical approaches for this
application, and identified some limitations and the extent to which these may be tractable
with more extensive sequence data and further development of analytical approaches. </p>
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