Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia

Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5491-6. doi: 10.1073/pnas.1502561112. Epub 2015 Apr 13.


The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.

Keywords: Borrelia; Lyme disease; cholesterol; relapsing fever; tick-borne.

Publication types

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

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency*
  • Borrelia burgdorferi / metabolism*
  • Cholesterol / blood*
  • Disease Models, Animal
  • Humans
  • Hypercholesterolemia* / blood
  • Hypercholesterolemia* / genetics
  • Hypercholesterolemia* / pathology
  • Lyme Disease* / blood
  • Lyme Disease* / genetics
  • Lyme Disease* / pathology
  • Mice
  • Mice, Knockout
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Relapsing Fever* / blood
  • Relapsing Fever* / genetics
  • Relapsing Fever* / pathology
  • Risk Factors


  • Apolipoproteins E
  • Receptors, LDL
  • Cholesterol