Evolution of chronic infection in Anasplasma phagocytophilum

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DESCRIPTION (provided by applicant): The tick-transmitted rickettsial pathogens Anaplasma phagocytophilum and A. marginale cause potentially fatal, acute or chronic disease of man and animals. The genomes of both bacteria contain contingency loci; the organisms interact with host immunity by recombination of functional pseudogenes into expression sites needing major surface antigens. These organisms represent valuable models for the study of coevolution because of variable levels of natural selection due to immunity imposed by hosts, obligate drift imposed by transmission through ticks and hosts, and strategies of hyper-recombination utilized by the pathogens. Despite theories of optimal recombination strategies for pathogenic bacteria, particular strategies are highly variable. Few studies have combined experimental, field, genomic, and theory-based research to investigate the evolution and emergence of new chronic infectious disease. Our long-term goals are to limit disease emergence through a study of molecular and evolutionary interactions between hosts, vectors and pathogens that lead to persistence. The specific aims are: 1. To determine if multiple closely-related strains of A. phagocytophilum with different host tropisms may circulate in natural ecosystems. 2. To sequence the genomes of the Hoopa WR and AP-variant 1 strains of A. phagocytophilum. 3. To experimentally describe the kinetics of infection by different strains of A. phagocytophilum in host species that typically undergoes persistent or limited infections, and 4. To model the evolution and emergence of A. phagocytophilum genospecies. The rationale is that field studies will document coevolved pathogen-host species associations; experimental research will show how reservoir and infection-limiting hosts differ in their imposition of natural selection via immunity; genome studies will reveal how the phenology of bacterial expression of surface antigens through hyper-recombination differs in these hosts; and theoretical modeling will integrate laboratory and field-collected data to investigate coevolutionary, microbiological, and ecological factors underlying the emergence and maintenance of A. phagocytophilum infection. Ultimately, understanding evolutionary factors in A. phagocytophilum-host interactions and disease mechanisms will contribute to our ability to control chronic infections caused by pathogenic bacteria and provide management approaches that limit the emergence of these and other vector-borne diseases.