Borrelia burgdorferi bbk13 Is Critical for Spirochete Population Expansion in the Skin during Early Infection

Infect Immun. 2019 Apr 23;87(5):e00887-18. doi: 10.1128/IAI.00887-18. Print 2019 Mar.


Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted via the bite of an infected tick. B. burgdorferi enters the skin, disseminates via the bloodstream, and infects various distal tissues, leading to inflammatory sequelae, such as Lyme arthritis and Lyme carditis. B. burgdorferi linear plasmid 36 (lp36) is critical for mammalian infectivity; however, the full complement of genes on lp36 that contribute to this process remains unknown. Through a targeted mutagenesis screen of the genes on lp36, we identified a novel infectivity gene of unknown function, bbk13, which encodes an immunogenic, non-surface-exposed membrane protein that is important for efficient mammalian infection. Loss of bbk13 resulted in reduced spirochete loads in distal tissues in a mouse model of infection. Through a detailed analysis of B. burgdorferi infection kinetics, we discovered that bbk13 is important for promoting spirochete proliferation in the skin inoculation site. The attenuated ability of Δbbk13 spirochetes to proliferate in the inoculation site was followed by reduced numbers of B. burgdorferi spirochetes in the bloodstream and, ultimately, consistently reduced spirochete loads in distal tissues. Together, our data indicate that bbk13 contributes to disseminated infection by promoting spirochete proliferation in the early phase of infection in the skin. This work not only increases the understanding of the contribution of the genes on lp36 to B. burgdorferi infection but also begins to define the genetic basis for B. burgdorferi expansion in the skin during localized infection and highlights the influence of the early expansion of spirochetes in the skin on the outcome of infection.

Keywords: Borrelia burgdorferi; Lyme disease; dissemination; lp36; skin; vector-borne disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / blood*
  • Bacterial Proteins / genetics
  • Borrelia burgdorferi / genetics*
  • Disease Models, Animal
  • Host-Parasite Interactions / genetics*
  • Lyme Disease / microbiology*
  • Lyme Disease / pathology*
  • Mice
  • Plasmids
  • Rabbits
  • Recombinant Proteins / genetics*
  • Virulence / genetics*


  • Bacterial Proteins
  • Recombinant Proteins