The absence of linear plasmid 25 or 28-1 of Borrelia burgdorferi dramatically alters the kinetics of experimental infection via distinct mechanisms

Infect Immun. 2003 Aug;71(8):4608-13. doi: 10.1128/iai.71.8.4608-4613.2003.

Abstract

The 25-kb linear plasmid lp25 and one of the 28-kb linear plasmids (lp28-1) are required for experimental infection in Borrelia burgdorferi, the etiologic agent of Lyme disease. The loss of these plasmids either eliminates infectivity (lp25) or significantly increases the 50% infective dose during a 2-week infection period (lp28-1). This study assessed the kinetics of bacterial dissemination in C3H/HeN mice infected with B. burgdorferi lacking either lp25 or lp28-1, as well as their wild-type parent, and tracked the development of specific borrelial antibodies over a 3-week period. The results indicated that the wild type and the lp28-1(-) strains were able to disseminate throughout the host, whereas the lp25(-) strain was cleared within 48 h of inoculation. While the wild-type B. burgdorferi persisted in tissues for the duration of the study, the lp28-1(-) mutant began clearing at day 8, with no detectable bacteria present by day 18. As expected, the wild-type strain persisted in C3H/HeN mice despite a strong humoral response; however, the lp28-1(-) mutant was cleared coincidently with the development of a modest immunoglobulin M response. The lp28-1(-) mutant was able to disseminate and persist in C3H-scid mice at a level indistinguishable from that of wild-type cells, confirming that acquired immunity was required for clearance in C3H/HeN mice. Thus, within an immunocompetent host, lp28-1-encoded proteins are not required for dissemination but are essential for persistence associated with Lyme borreliosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Borrelia burgdorferi / genetics*
  • Borrelia burgdorferi / immunology
  • Borrelia burgdorferi / isolation & purification
  • Borrelia burgdorferi / pathogenicity*
  • Female
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin M / biosynthesis
  • Kinetics
  • Lyme Disease / etiology*
  • Lyme Disease / microbiology
  • Mice
  • Mice, Inbred C3H
  • Mice, SCID
  • Mutation
  • Plasmids / genetics*
  • Virulence / genetics

Substances

  • Antibodies, Bacterial
  • Immunoglobulin G
  • Immunoglobulin M