Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

J Clin Invest. 2009 Dec;119(12):3652-65. doi: 10.1172/JCI39401. Epub 2009 Nov 16.


Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination "adherence-mediated migration" and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Borrelia burgdorferi / genetics
  • Borrelia burgdorferi / isolation & purification
  • Borrelia burgdorferi / pathogenicity*
  • Borrelia burgdorferi / physiology
  • Digestive System / microbiology
  • Female
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Humans
  • Ixodes / anatomy & histology
  • Ixodes / growth & development
  • Ixodes / microbiology*
  • Lyme Disease / microbiology
  • Lyme Disease / transmission
  • Mice
  • Mice, Inbred C3H
  • Recombinant Proteins / genetics
  • Salivary Glands / microbiology
  • Virulence / genetics
  • Virulence / physiology


  • Recombinant Proteins
  • Green Fluorescent Proteins