title: Borrelia burgdorferi OspC protein required exclusively in a crucial early stage of mammalian infection.
abstract: This study demonstrates a strict temporal requirement for a virulence determinant of the Lyme disease spirochete Borrelia burgdorferi during a unique point in its natural infection cycle, which alternates between ticks and small mammals. OspC is a major surface protein produced by B. burgdorferi when infected ticks feed but whose synthesis decreases after transmission to a mammalian host. We have previously shown that spirochetes lacking OspC are competent to replicate in and migrate to the salivary glands of the tick vector but do not infect mice. Here we assessed the timing of the requirement for OspC by using an ospC mutant complemented with an unstable copy of the ospC gene and show that B. burgdorferi's requirement for OspC is specific to the mammal and limited to a critical early stage of mammalian infection. By using this unique system, we found that most bacterial reisolates from mice persistently infected with the initially complemented ospC mutant strain no longer carried the wild-type copy of ospC. Such spirochetes were acquired by feeding ticks and migrated to the tick salivary glands during subsequent feeding. Despite normal behavior in ticks, these ospC mutant spirochetes did not infect naive mice. ospC mutant spirochetes from persistently infected mice also failed to infect naive mice by tissue transplantation. We conclude that OspC is indispensable for establishing infection by B. burgdorferi in mammals but is not required at any other point of the mouse-tick infection cycle.
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840, USA. ktilly@nih.gov
authors.forename: Kit
authors.initials: K
authors.lastname: Tilly
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Krum
authors.forename: Aaron
authors.initials: A
authors.lastname: Bestor
authors.forename: Mollie W
authors.initials: MW
authors.lastname: Jewett
authors.forename: Dorothee
authors.initials: D
authors.lastname: Grimm
authors.forename: Dawn
authors.initials: D
authors.lastname: Bueschel
authors.forename: Rebecca
authors.initials: R
authors.lastname: Byram
authors.forename: David
authors.initials: D
authors.lastname: Dorward
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Vanraden
authors.forename: Philip
authors.initials: P
authors.lastname: Stewart
authors.forename: Patricia
authors.initials: P
authors.lastname: Rosa
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000472:pathogenicity*; D008193:Lyme Disease / Q000209:etiology* / Q000382:microbiology / Q000635:transmission; D051379:Mice; D008809:Mice, Inbred C3H; D010641:Phenotype; D010957:Plasmids; D016133:Polymerase Chain Reaction; D013987:Ticks / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C079616:OspC protein