ABSTRACT
There is strong epidemiologic evidence of human adaption of the zoonotic pathogen Campylobacter. However,
the genomic features of such adaptation have not been systematically evaluated. The overall objective of this
project is to identify specific genomic features of Campylobacter that are associated with adaptation to the
human host with the long-term goal of applying this knowledge to global reference databases to inform host
attribution and guide improved disease control measures to reduce the global burden of Campylobacter
disease in humans. Our central hypothesis is that in highly endemic settings, long-term exposure has allowed
adaptation to the human host, as opposed to the transient infection epidemiology we usually observe with
Campylobacter. Previous evidence of human adaption has been previously suggested by prolonged carriage in
immunosuppressed patients and that certain Campylobacter lineages associated with human disease and
chronic sequelae such as GBS, are rarely found outside the human host. We have identified these
observations in two longitudinal cohort studies in the Peruvian Amazon that cumulatively comprise over 1400
child-years of surveillance, 20,000 stool samples and 850 Campylobacter isolates. Specifically, we evidence a)
persistent Campylobacter infection and carriage in over 70% of children with complete 0 to 24-month follow-up,
b) high-level of C. jejuni strain diversity derived from humans compared to the global collection of clinical
genomes, c) high proportion of strains described exclusively in human hosts (such ST-403, ST2802 and ST-
2993), as compared to the global reference collection and d) considerable reduced genome size of human
derived C. jejuni genomes compared to the global reference collection. In order to test our hypothesis, we will
1) Identify genomic features of persistent Campylobacter infections in humans, and 2) Determine if
spatiotemporally clustered infections represent human to human transmission. The proposed project will unite
a highly complementary group of accomplished researchers with expertise in epidemiology, evolutionary
biology, Campylobacter genomics, and bioinformatics to inform strategic and targeted disease control
interventions for Campylobacter control in an area with one of the highest documented rates of human MDR
Campylobacter infection. [The project is innovative in the way it applies microbial GWAS methods to capitalize
on an exceptional strain bank derived from well-defined longitudinal cohort studies to efficiently identify host
adaptation.] [High quality evidence of human host adaptation generated by this study would be paradigm
shifting to strategies used to control Campylobacter and would likely to alter the clinical management of
Campylobacter enteritis.]