title: Postgenomic analyses reveal development of infectious Anaplasma phagocytophilum during transmission from ticks to mice.
abstract: Obligate intracellular bacteria of the Rickettsiales order have evolved to colonize both arthropod and mammalian hosts, but few details are known about the bacterial adaptations that occur during transmission from blood-feeding arthropods to mammals. Here we apply proteomics and transcriptome sequencing to Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, in Ixodes scapularis tick salivary glands, to detect proteins or genes expressed by the pathogen during transmission feeding by the tick. We detected expression of 139 genes, representing 11% of the open reading frames (ORFs) in the A. phagocytophilum genome. The predominant categories of proteins were ribosomal proteins, cell surface proteins, chaperones, and uncharacterized proteins. There was no evidence of DNA replication enzymes, suggesting that most of the A. phagocytophilum cells were no longer dividing. Instead, protein expression reflected conversion to the extracellular, infectious "dense-core" (DC) form. High expression of a DC-specific marker, APH_1235, further suggested this developmental transition in ticks. We showed that blocking APH_1235 with antibodies reduced A. phagocytophilum infection levels in mammalian cell culture. This work represents a starting point for clarifying essential proteins expressed by A. phagocytophilum during transmission from ticks to mammals and demonstrates that the abundantly expressed, DC-associated APH_1235 protein is important during in vivo infection by A. phagocytophilum.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. juliana.mastronunzio@gmail.com
authors.forename: Juliana E
authors.initials: JE
authors.lastname: Mastronunzio
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kurscheid
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D041081:Anaplasma phagocytophilum / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins; D002244:Carbon / Q000378:metabolism; D016873:Ehrlichiosis / Q000382:microbiology; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D018884:Ixodes / Q000382:microbiology*; D007814:Larva / Q000382:microbiology; D051379:Mice; D009758:Nymph / Q000382:microbiology; D012329:RNA, Bacterial; D012469:Salivary Glands / Q000382:microbiology; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D002244:Carbon