title: Anaplasma marginale Actively Modulates Vacuolar Maturation during Intracellular Infection of Its Tick Vector, Dermacentor andersoni.
abstract: Tick-borne transmission of bacterial pathogens in the order Rickettsiales is responsible for diverse infectious diseases, many of them severe, in humans and animals. Transmission dynamics differ among these pathogens and are reflected in the pathogen-vector interaction. Anaplasma marginale has been shown to establish and maintain infectivity within Dermacentor spp. for weeks to months while escaping the complex network of vacuolar peptidases that are responsible for digestion of the tick blood meal. How this prolonged maintenance of infectivity in a potentially hostile environment is achieved has been unknown. Using the natural vector Dermacentor andersoni, we demonstrated that A. marginale-infected tick vacuoles (AmVs) concurrently recruit markers of the early endosome (Rab5), recycling endosome (Rab4 and Rab11), and late endosome (Rab7), are maintained near neutral pH, do not fuse with lysosomes, exclude the protease cathepsin L, and engage the endoplasmic reticulum and Golgi apparatus for up to 21 days postinfection. Maintenance of this safe vacuolar niche requires active A. marginale protein synthesis; in its absence, the AmVs mature into acidic, protease-active phagolysosomes. Identification of this bacterially directed modeling of the tick midgut endosome provides a mechanistic basis for examination of the differences in transmission efficiency observed among A. marginale strains and among vector populations.
  
  
  
  Ticks transmit a variety of intracellular bacterial pathogens that cause significant diseases in humans and animals. For successful transmission, these bacterial pathogens must first gain entry into the tick midgut digestive cells, avoid digestion, and establish a replicative niche without harming the tick vector. Little is known about how this replicative niche is established and maintained. Using the ruminant pathogen A. marginale and its natural tick vector, D. andersoni, this study characterized the features of the A. marginale niche in the tick midgut and demonstrates that A. marginale protein synthesis is required for the maintenance of this niche. This work opens a new line of inquiry about the pathogen effectors and their targets within the tick that mediate tick-pathogen interactions and ultimately serve as the determinants of pathogen success.
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, Washington, USA magundaf@vetmed.wsu.edu.|Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.|Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA.
authors.forename: Forgivemore
authors.identifier: http://orcid.org/0000-0001-7854-5818
authors.initials: F
authors.lastname: Magunda
authors.affiliation: Old Dominion University, Department of Biological Sciences, Norfolk, Virginia, USA.
authors.forename: Chelsea Wright
authors.initials: CW
authors.lastname: Thompson
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, Washington, USA.|Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Schneider
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, Washington, USA.|Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.|Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Noh
mesh_terms: D042322:Anaplasma marginale / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D000818:Animals; D001096:Arachnid Vectors / Q000378:metabolism / Q000382:microbiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000382:microbiology; D003870:Dermacentor / Q000378:metabolism / Q000382:microbiology*; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins