title: A tick gut protein with fibronectin III domains aids Borrelia burgdorferi congregation to the gut during transmission.
abstract: Borrelia burgdorferi transmission to the vertebrate host commences with growth of the spirochete in the tick gut and migration from the gut to the salivary glands. This complex process, involving intimate interactions of the spirochete with the gut epithelium, is pivotal to transmission. We utilized a yeast surface display library of tick gut proteins to perform a global screen for tick gut proteins that might interact with Borrelia membrane proteins. A putative fibronectin type III domain-containing tick gut protein (Ixofin3D) was most frequently identified from this screen and prioritized for further analysis. Immunization against Ixofin3D and RNA interference-mediated reduction in expression of Ixofin3D resulted in decreased spirochete burden in tick salivary glands and in the murine host. Microscopic examination showed decreased aggregation of spirochetes on the gut epithelium concomitant with reduced expression of Ixofin3D. Our observations suggest that the interaction between Borrelia and Ixofin3D facilitates spirochete congregation to the gut during transmission, and provides a "molecular exit" direction for spirochete egress from the gut.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Narasimhan
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Coumou
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Schuijt
authors.affiliation: Department of Chemical and Biomolecular of Engineering, University of Tennessee, Knoxville, Tennessee, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Boder
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Joppe W
authors.initials: JW
authors.lastname: Hovius
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000818:Animals; D060829:Arthropod Proteins / Q000378:metabolism*; D025065:Borrelia burgdorferi; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism*; D006790:Host-Parasite Interactions / Q000502:physiology*; D008193:Lyme Disease / Q000635:transmission*; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013987:Ticks / Q000378:metabolism*
chemical_list: D060829:Arthropod Proteins; D005353:Fibronectins
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