Evolution of chronic infection in Anasplasma phagocytophilum

Summary

Principal Investigator: Anthony Barbet
Abstract: 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.
Funding Period: ----------------2007 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Vector biodiversity did not associate with tick-borne pathogen prevalence in small mammal communities in northern and central California
    Janet Foley
    School of Veterinary Medicine, Department of Medicine and Epidemiology, University of California, Davis, CA 95616, USA Electronic address
    Ticks Tick Borne Dis 5:299-304. 2014
  2. pmc Unique strains of Anaplasma phagocytophilum segregate among diverse questing and non-questing Ixodes tick species in the western United States
    Daniel Rejmanek
    Davis School of Veterinary Medicine, University of California, Department of Medicine and Epidemiology, Davis, CA 95616, USA Electronic address
    Ticks Tick Borne Dis 4:482-7. 2013
  3. ncbi Anaplasma phagocytophilum in ticks from parks in the Emilia-Romagna region of northern Italy
    Sara Aureli
    Department of Veterinary Medical Sciences, Alma Mater Studiorum University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Bologna, Italy
    Vet Ital 48:413-23. 2012
  4. pmc Structure of the type IV secretion system in different strains of Anaplasma phagocytophilum
    Basima Al-Khedery
    Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
    BMC Genomics 13:678. 2012
  5. pmc Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host
    Daniel Rejmanek
    University of California, Davis School of Veterinary Medicine, Department of Medicine and Epidemiology, Davis, CA 95616, USA
    Microbiology 158:2632-41. 2012
  6. pmc Determining the repertoire of immunodominant proteins via whole-genome amplification of intracellular pathogens
    Michael J Dark
    Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA
    PLoS ONE 7:e36456. 2012
  7. pmc Nidicolous ticks of small mammals in Anaplasma phagocytophilum-enzootic sites in northern California
    Janet Foley
    University of California, Davis School of Veterinary Medicine, Dept of Medicine and Epidemiology, Davis, CA 95616, USA
    Ticks Tick Borne Dis 2:75-80. 2011
  8. pmc Evolution of antigen variation in the tick-borne pathogen Anaplasma phagocytophilum
    Daniel Rejmanek
    Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA
    Mol Biol Evol 29:391-400. 2012
  9. pmc Molecular characterization reveals distinct genospecies of Anaplasma phagocytophilum from diverse North American hosts
    Daniel Rejmanek
    University of California, Davis School of Veterinary Medicine, Department of Medicine and Epidemiology, Davis, CA 95616, USA
    J Med Microbiol 61:204-12. 2012
  10. pmc The ecology of tick-transmitted infections in the redwood chipmunk (Tamias ochrogenys)
    Janet E Foley
    University of California, Davis School of Veterinary Medicine, Department of Medicine and Epidemiology, Davis, CA 95616, USA
    Ticks Tick Borne Dis 2:88-93. 2011

Scientific Experts

Detail Information

Publications17

  1. pmc Vector biodiversity did not associate with tick-borne pathogen prevalence in small mammal communities in northern and central California
    Janet Foley
    School of Veterinary Medicine, Department of Medicine and Epidemiology, University of California, Davis, CA 95616, USA Electronic address
    Ticks Tick Borne Dis 5:299-304. 2014
    ..No particular tick species was likely to "rescue" infection in the community; rather the risk of A. phagocytophilum infection is related to exposure to particular tick species and life stages, and overall tick abundance. ..
  2. pmc Unique strains of Anaplasma phagocytophilum segregate among diverse questing and non-questing Ixodes tick species in the western United States
    Daniel Rejmanek
    Davis School of Veterinary Medicine, University of California, Department of Medicine and Epidemiology, Davis, CA 95616, USA Electronic address
    Ticks Tick Borne Dis 4:482-7. 2013
    ....
  3. ncbi Anaplasma phagocytophilum in ticks from parks in the Emilia-Romagna region of northern Italy
    Sara Aureli
    Department of Veterinary Medical Sciences, Alma Mater Studiorum University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Bologna, Italy
    Vet Ital 48:413-23. 2012
    ..phagocytophilum in northern Italy and would provide valuable information on zoonotic risks...
  4. pmc Structure of the type IV secretion system in different strains of Anaplasma phagocytophilum
    Basima Al-Khedery
    Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
    BMC Genomics 13:678. 2012
    ..We determined the structure of the T4SS in 7 strains from the U.S. and Europe and revised the sequence of the repetitive virB6 locus of the human HZ strain...
  5. pmc Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host
    Daniel Rejmanek
    University of California, Davis School of Veterinary Medicine, Department of Medicine and Epidemiology, Davis, CA 95616, USA
    Microbiology 158:2632-41. 2012
    ..Our findings suggest a tightly co-evolved relationship between A. phagocytophilum and woodrats in which the pathogen perpetually evades host immunity yet causes no detectable disease...
  6. pmc Determining the repertoire of immunodominant proteins via whole-genome amplification of intracellular pathogens
    Michael J Dark
    Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA
    PLoS ONE 7:e36456. 2012
    ..Additionally, all msp2 functional pseudogenes from two strains of A. marginale were detected and extracted from the phi29-amplified genomes, highlighting its utility in determining the full complement of genes involved in immune evasion...
  7. pmc Nidicolous ticks of small mammals in Anaplasma phagocytophilum-enzootic sites in northern California
    Janet Foley
    University of California, Davis School of Veterinary Medicine, Dept of Medicine and Epidemiology, Davis, CA 95616, USA
    Ticks Tick Borne Dis 2:75-80. 2011
    ..Overall, we show high tick species richness and year-round high levels of infestation on rodents by several different nidicolous ticks in areas where A. phagocytophilum is enzootic, including on reported reservoir species...
  8. pmc Evolution of antigen variation in the tick-borne pathogen Anaplasma phagocytophilum
    Daniel Rejmanek
    Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA
    Mol Biol Evol 29:391-400. 2012
    ..phagocytophilum may comprise random genetic drift as well as some innate but apparently nonpurifying selection prior to the strong frequency-dependent selection that occurs cyclically after hosts develop strong adaptive immunity...
  9. pmc Molecular characterization reveals distinct genospecies of Anaplasma phagocytophilum from diverse North American hosts
    Daniel Rejmanek
    University of California, Davis School of Veterinary Medicine, Department of Medicine and Epidemiology, Davis, CA 95616, USA
    J Med Microbiol 61:204-12. 2012
    ..Our findings indicate that multiple unique strains of A. phagocytophilum with distinct host tropisms exist in California. Future epidemiological studies evaluating human and domestic animal risk should incorporate these distinctions...
  10. pmc The ecology of tick-transmitted infections in the redwood chipmunk (Tamias ochrogenys)
    Janet E Foley
    University of California, Davis School of Veterinary Medicine, Department of Medicine and Epidemiology, Davis, CA 95616, USA
    Ticks Tick Borne Dis 2:88-93. 2011
    ..The biology of the redwood chipmunk has multiple features that allow it to be an important reservoir host for tick-borne disease in northwestern California...
  11. ncbi The dusky-footed woodrat (Neotoma fuscipes) is susceptible to infection by Anaplasma phagocytophilum originating from woodrats, horses, and dogs
    Nathan C Nieto
    Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
    J Wildl Dis 46:810-7. 2010
    ..phagocytophilum, resulting in clinical anaplasmosis. Our data show that woodrats are permissive to several strains of A. phagocytophilum, but strains originating from woodrats did not cause clinical disease in horses...
  12. ncbi Coinfection of western gray squirrel (Sciurus griseus) and other sciurid rodents with Borrelia burgdorferi sensu stricto and Anaplasma phagocytophilum in California
    Nathan C Nieto
    Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California 95616, USA
    J Wildl Dis 46:291-6. 2010
    ....
  13. pmc Antigen diversity in the parasitic bacterium Anaplasma phagocytophilum arises from selectively-represented, spatially clustered functional pseudogenes
    Janet E Foley
    Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California, USA
    PLoS ONE 4:e8265. 2009
    ....
  14. doi Tularemia
    Janet E Foley
    Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
    Vet Microbiol 140:332-8. 2010
    ..We discuss microbiological, clinicopathological, epidemiological, and ecological aspects of tularemia...
  15. pmc Diversity of Anaplasma phagocytophilum strains, USA
    Eric Morissette
    University of Florida, Gainesville, Florida 32611 0880, USA
    Emerg Infect Dis 15:928-31. 2009
    ..The sequence of p44ESup1 had diverged in Ap-variant 1 strains infecting ruminants. In contrast, no differences were detected between A. phagocytophilum strains infecting humans and domestic dogs...
  16. pmc varDB: common ground for a shifting landscape
    David R Allred
    Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32611, USA
    Trends Parasitol 25:249-52. 2009
    ..A critique of this database and how it could serve the scientific community is provided here...