Genomic features of host adaptation of Campylobacter in low-income settings

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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.]