title: OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands.
abstract: Outer surface protein C (OspC) is a differentially expressed major surface lipoprotein of Borrelia burgdorferi. ospC is swiftly upregulated when spirochetes leave the Ixodes scapularis tick gut, migrate to the salivary gland, and exit the arthropod vector. Here we show that OspC strongly binds to the tick salivary gland, suggesting a role for OspC in spirochete adherence to this tissue. In vivo studies using a murine model of Lyme borreliosis showed that while OspC F(ab)(2) fragments did not influence either the viability of spirochetes or ospC gene expression, they did interfere with B. burgdorferi invasion of tick salivary glands. We then generated ospC knockout spirochetes in an infectious clone of B. burgdorferi and examined them within the vector. OspC-deficient or wild-type spirochetes persisted equally within the gut of unfed ticks and multiplied during the tick engorgement; however, unlike wild-type B. burgdorferi, the mutants were unable to invade salivary glands. Salivary gland colonization of OspC-deficient spirochetes was completely restored when this mutant was complemented in trans with a plasmid harboring the wild-type ospC gene. These studies conclusively demonstrate the importance of OspC in the invasion of tick salivary glands by B. burgdorferi, a critical step in the transmission of spirochetes from the arthropod vector to the mammalian host.
authors.affiliation: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Utpal
authors.initials: U
authors.lastname: Pal
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.forename: Manchuan
authors.initials: M
authors.lastname: Chen
authors.forename: Linda K
authors.initials: LK
authors.lastname: Bockenstedt
authors.forename: John F
authors.initials: JF
authors.lastname: Anderson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Michael V
authors.initials: MV
authors.lastname: Norgard
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000472:pathogenicity*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D018884:Ixodes / Q000382:microbiology*; D008074:Lipoproteins / Q000737:chemistry; D008193:Lyme Disease / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000378:metabolism / Q000382:microbiology*; D013144:Spirochaetales / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000199:Actins; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007140:Immunoglobulin Fab Fragments; D008074:Lipoproteins; C079616:OspC protein; D011994:Recombinant Proteins