title: Pathogen-mediated manipulation of arthropod microbiota to promote infection.
abstract: Arthropods transmit diverse infectious agents; however, the ways microbes influence their vector to enhance colonization are poorly understood. Ixodes scapularis ticks harbor numerous human pathogens, including Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. We now demonstrate that A. phagocytophilum modifies the I. scapularis microbiota to more efficiently infect the tick. A. phagocytophilum induces ticks to express Ixodes scapularis antifreeze glycoprotein (iafgp), which encodes a protein with several properties, including the ability to alter bacterial biofilm formation. IAFGP thereby perturbs the tick gut microbiota, which influences the integrity of the peritrophic matrix and gut barrier-critical obstacles for Anaplasma colonization. Mechanistically, IAFGP binds the terminal d-alanine residue of the pentapeptide chain of bacterial peptidoglycan, resulting in altered permeability and the capacity of bacteria to form biofilms. These data elucidate the molecular mechanisms by which a human pathogen appropriates an arthropod antibacterial protein to alter the gut microbiota and more effectively colonize the vector.
authors.affiliation: Section of Infectious Disease, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.|Howard Hughes Medical Institute, Chevy Chase, MD 20815.
authors.forename: Nabil M
authors.initials: NM
authors.lastname: Abraham
authors.affiliation: Section of Infectious Disease, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510; lei.liu.ll69@yale.edu erol.fikrig@yale.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815.|Microbial Sciences Institute, Yale University, West Haven, CT 06516.|Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520.
authors.forename: Brandon Lyon
authors.initials: BL
authors.lastname: Jutras
authors.affiliation: Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Umeå Center for Microbial Research, Umeå University, 901 87 Umea, Sweden.
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Section of Infectious Disease, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Narasimhan
authors.affiliation: Section of Infectious Disease, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.|Howard Hughes Medical Institute, Chevy Chase, MD 20815.|Rush Medical College, Rush University Medical Center, Chicago, IL 60612.
authors.forename: Vissagan
authors.initials: V
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Biology, Fairfield University, Fairfield, CT 06824.
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Ansari
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Jefferson
authors.affiliation: Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Umeå Center for Microbial Research, Umeå University, 901 87 Umea, Sweden.
authors.forename: Felipe
authors.initials: F
authors.lastname: Cava
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815.|Microbial Sciences Institute, Yale University, West Haven, CT 06516.|Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520.|Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520.
authors.forename: Christine
authors.initials: C
authors.lastname: Jacobs-Wagner
authors.affiliation: Section of Infectious Disease, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510; lei.liu.ll69@yale.edu erol.fikrig@yale.edu.|Howard Hughes Medical Institute, Chevy Chase, MD 20815.|Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520.
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D041081:Anaplasma phagocytophilum / Q000502:physiology*; D000818:Animals; D021301:Antifreeze Proteins / Q000378:metabolism; D060829:Arthropod Proteins / Q000378:metabolism; D016873:Ehrlichiosis; D000069196:Gastrointestinal Microbiome; D054884:Host-Pathogen Interactions; D018884:Ixodes / Q000382:microbiology*; D051379:Mice; D010457:Peptidoglycan / Q000378:metabolism
chemical_list: D021301:Antifreeze Proteins; D060829:Arthropod Proteins; D010457:Peptidoglycan
keywords: Anaplasma; Ixodes scapularis; antifreeze protein; biofilm; microbiome